Red blood cell processing systems and methods with deliberate under spill of red blood cells

ABSTRACT

Collection systems and methods use a separation chamber that receives blood or a suspension containing red blood cells and performs a separation process including separation of red blood cells from the blood or suspension. The separation chamber contains, during the separation process, a red blood cell volume. An outlet line is coupled to the separation chamber to remove red blood cells from the chamber device, at least in part, while the separation process occurs. A collection container is coupled to the outlet line to receive a volume of red blood cells removed from the separation chamber. A controller includes a processing function that, during the separation process, includes comparing the volume of red blood cells received by the collection container to a selected targeted red blood cell collection volume to derive a difference. The controller includes another processing function that includes purging substantially all the red blood cell volume occupying the separation chamber into the collection container when the red blood cell volume occupying the separation chamber approximates the difference.

RELATED APPLICATIONS

[0001] This application claims the benefit of co-pending U.S.application Ser. No. 09/931,146 filed Aug. 16, 2001, and entitled“Sensing Systems and Methods for Differentiating Between DifferentCellular Blood Species During Extracorporeal Blood Separation orProcessing”.

FIELD OF THE INVENTION

[0002] This invention relates to systems and methods for processing andcollecting blood, blood constituents, or other suspensions of cellularmaterial.

BACKGROUND OF THE INVENTION

[0003] Today people routinely separate whole blood, usually bycentrifugation, into its various therapeutic components, such as redblood cells, platelets, and plasma.

[0004] Conventional blood processing methods use durable centrifugeequipment in association with single use, sterile processing systems,typically made of plastic. The operator loads the disposable systemsupon the centrifuge before processing and removes them afterwards.

[0005] Conventional blood centrifuges are of a size that does not permiteasy transport between collection sites. Furthermore, loading andunloading operations can sometimes be time consuming and tedious.

[0006] In addition, a need exists for further improved systems andmethods for collecting blood components in a way that lends itself touse in high volume, on line blood collection environments, where higheryields of critically needed cellular blood components, like plasma, redblood cells, and platelets, can be realized in reasonable shortprocessing times.

[0007] The operational and performance demands upon such fluidprocessing systems become more complex and sophisticated, even as thedemand for smaller and more portable systems intensifies. The needtherefore exists for automated blood processing controllers that cangather and generate more detailed information and control signals to aidthe operator in maximizing processing and separation efficiencies.

SUMMARY OF THE INVENTION

[0008] One aspect of the invention provides collection systems andmethods that use a separation chamber that receives blood or asuspension containing red blood cells and performs a separation processincluding separation of red blood cells from the blood or suspension.The separation chamber contains, during the separation process, a redblood cell volume. An outlet line is coupled to the separation chamberto remove red blood cells from the chamber device, at least in part,while the separation process occurs. A collection container is coupledto the outlet line to receive a volume of red blood cells removed fromthe separation chamber. According to this aspect of the invention, acontroller includes a processing function that, during the separationprocess, includes comparing the volume of red blood cells received bythe collection container to a selected targeted red blood cellcollection volume to derive a difference. The controller includesanother processing function that includes purging-substantially all thered blood cell volume occupying the separation chamber into thecollection container when the red blood cell volume occupying theseparation chamber approximates the difference.

[0009] According to this aspect of the invention, the controller canshorten the overall procedure time by causing a forced under spill ofred blood cells from the separation chamber into the red blood cellcollection container near the end of the procedure. The deliberatelyforced under spill serves to purge residual red blood cell volume fromthe separation chamber at the end of a procedure, thereby simplifyingand shortening the time of collection and the final red blood cellreturn cycle.

[0010] Other features and advantages of the inventions are set forth inthe following specification and attached drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0011]FIG. 1 is a perspective view of a fluid processing system, ideallysuited for blood processing, comprising a blood processing device (shownin a closed condition for transport and storage) and a disposable liquidand blood flow set, which interacts with the blood processing device tocause separation and collection of one or more blood components (shownpackaged in a tray for transport and storage before use).

[0012]FIG. 2 is a perspective view of the blood processing device shownin FIG. 1, shown in an opened condition for operation.

[0013]FIG. 3 is a perspective view of the blood processing device shownin FIG. 2, with the centrifugal station open to receive a bloodprocessing chamber and the pump and valve station open to receive afluid pressure-actuated cassette.

[0014]FIG. 4 is a perspective view of the blood processing device shownin FIG. 3, with the tray containing the disposable liquid and blood flowset positioned for loading the flow set on the device.

[0015]FIGS. 5 and 6 are, respectively, right and left side perspectiveviews of the blood processing device shown in FIG. 2 after the liquidand blood flow set has been loaded onto the device for use.

[0016]FIG. 7 is a perspective view of the blood processing chamber andattached umbilicus that forms a part of the liquid and blood flow setshown in FIGS. 5 and 6.

[0017]FIG. 8 is a perspective view of the interior of a representativeembodiment of the blood processing chamber of a type shown in FIG. 7,the interior of the chamber being configured to perform a red blood cellseparation and collection procedure using the device shown in FIGS. 5and 6.

[0018]FIG. 9 is a perspective view of the interior of the centrifugestation of the device shown in FIGS. 5 and 6, with the station dooropened to receive a blood processing chamber of a type shown in FIG. 7.

[0019]FIG. 10 is a perspective view of the interior of the centrifugestation shown in FIG. 9 after a blood processing chamber of a type shownin FIG. 7 has been loaded for use.

[0020]FIG. 11A is an enlarged perspective view of a fixture that iscarried by the umbilicus shown in FIG. 7, showing its intendedassociation with an optical sensing station that forms a part of thedevice shown in FIGS. 5 and 6.

[0021]FIG. 11B is a side section view of the optical sensing stationshown in FIG. 11A.

[0022]FIG. 11C is an exploded perspective view of the optical sensingstation shown in FIG. 11A.

[0023]FIG. 11D is a top view of the optical sensing station shown inFIG. 11A.

[0024]FIGS. 11E and 11F are schematic views of a circuit that can beused in association with the optical sensing station shown in FIG. 11A.

[0025]FIG. 12 is a diagrammatic view of the interior of the bloodprocessing chamber of a type shown in FIG. 7, showing the separation ofwhole blood into a red blood cell layer, a plasma layer, and anintermediate buffy coat layer, with the position of the layers shown ina desired relationship.

[0026]FIG. 13 is a diagrammatic view of the interior of the bloodprocessing chamber of a type shown in FIG. 7, with the buffy coat layerhaving moved very close to the low-G wall, creating an undesired overspill condition that sweeps buffy coat components into the plasma beingcollected.

[0027]FIG. 14 is a diagrammatic view of the interior of the bloodprocessing chamber of a type shown in FIG. 7, with the buffy coat layerhaving moved very close to the high-G wall, creating an undesired underspill condition that leads to a reduction of the hematocrit of red bloodbeing collected.

[0028]FIG. 15 is an exploded perspective view of the fluidpressure-actuated cassette that forms a part of the liquid and bloodflow set shown in FIGS. 5 and 6 and its operative association with thepump and valve station on the device, also shown in FIGS. 5 and 6, whichapplies positive and negative pneumatic pressure to the cassette tocirculate liquid and blood through the cassette.

[0029]FIG. 16 is a schematic view of a fluid circuit that can beimplemented in the cassette shown in FIG. 15 to enable the performanceof different blood processing and collection procedures.

[0030]FIG. 17 is a plane view of a cassette in which the fluid circuitshown in FIG. 17 is implemented.

[0031]FIG. 18 is a top perspective view of the interior of arepresentative embodiment of the blood processing chamber of a typeshown in FIG. 7, the interior of the chamber being configured to performa plasma separation and collection procedure using the device shown inFIGS. 5 and 6.

[0032]FIG. 19 is a bottom perspective view of the blood processingchamber shown in FIG. 18.

[0033]FIG. 20 is an enlarged side perspective view of an interior regionin the blood processing chamber shown in FIG. 18, showing a barrierhaving a tapered surface that directs red blood cells from theseparation zone in a path separate from plasma.

[0034]FIG. 21 is an enlarged bottom perspective view of the region shownin FIG. 20, showing the path that red blood cells take as they aredirected from the separation zone by the barrier.

[0035]FIG. 22 is an enlarged top perspective view of the region shown inFIG. 20, showing the separate paths that red blood cells and plasma takeas they are directed from the separation zone by the barrier.

[0036]FIG. 23 is a schematic view of a cassette of a type shown in FIGS.16 and 17 coupled to a liquid and blood flow set in a configuration thatcan be used for a plasma collection procedure.

[0037]FIG. 24 is a schematic view of a cassette of a type shown in FIGS.16 and 17 coupled to a liquid and blood flow set in a configuration thatcan be used for a double unit red blood cell collection procedure, theblood flow set also being shown in FIGS. 5 and 6 after being loaded onthe blood processing device.

[0038]FIGS. 25A and 25B are schematic views of the fluid circuit shownin FIG. 16 being conditioned by application of positive and negativepneumatic pressures to transport air in a controlled manner thatverifies that tubing intended to convey blood and liquids to and fromthe donor has been properly installed on the device, as shown in FIGS. 5and 6.

[0039]FIGS. 26A and 26B are schematic views of the fluid circuit shownin FIG. 16 being conditioned by application of positive and negativepneumatic pressures to transport air in a controlled manner thatverifies that tubing intended to convey anticoagulant into blood drawnfrom the donor has been properly installed on the device, as shown inFIGS. 5 and 6.

[0040] FIGS. 27 to 29 are schematic views of the fluid circuit shown inFIG. 16 being conditioned by application of positive and negativepneumatic pressures to transport a liquid in a controlled manner thatverifies the physical integrity of the cassette prior to use.

[0041] The invention may be embodied in several forms without departingfrom its spirit or essential characteristics. The scope of the inventionis defined in the appended claims, rather than in the specificdescription preceding them. All embodiments that fall within the meaningand range of equivalency of the claims are therefore intended to beembraced by the claims.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0042]FIG. 1 shows a fluid processing system 10 that embodies thefeatures of the invention. The system 10 can be used for processingvarious fluids.

[0043] The system 10 is particularly well suited for processing wholeblood and other suspensions of biological cellular materials.Accordingly, the illustrated embodiment shows the system 10 used forthis purpose.

I. System Overview

[0044] The system 10 includes two principal components. These are: (i) ablood processing device 14—shown in FIG. 1 in a closed condition fortransport and storage, and in FIGS. 2 and 3 in an opened condition foroperation); and (ii) a liquid and blood flow set 12, which interactswith the blood processing device 14 to cause separation and collectionof one or more blood components—the set 12 being shown in FIGS. 1 and 4packaged in a tray 48 for transport and storage before use, and in FIGS.5 and 6 removed from the tray 48 and mounted on the blood processingdevice 14 for use.

A. The Processing Device

[0045] The blood processing device 14 is intended to be a durable itemcapable of long term use. In the illustrated and preferred embodiment,the blood processing device 14 is mounted inside a portable housing orcase 36. The case 36 presents a compact footprint, suited for set up andoperation upon a table top or other relatively small surface. The case36 is also intended to be transported easily to a collection site.

[0046] The case 36 includes a base 38 and a hinged lid 40, which closesfor transport (as FIG. 1 shows) and which opens for use (as FIGS. 2 to 4show). In use, the base 38 is intended to rest in a generally horizontalsupport surface. The case 36 can be formed into a desired configuration,e.g., by molding. The case 36 is preferably made from a lightweight, yetdurable, plastic material.

[0047] A controller 16 is carried onboard the device 14. The controller16 governs the interaction between the components of the device 14 andthe components of the flow set 12 to perform a blood processing andcollection procedure selected by the operator. In the illustratedembodiment, the controller 16 comprises a main processing unit (MPU),which can comprise, e.g., a Pentium™ type microprocessor made by IntelCorporation, although other types of conventional microprocessors can beused. The MPU can be mounted inside the lid 40 of the case 36. A powersupply with power cord 184 supplies electrical power to the MPU andother components of the device 14.

[0048] Preferably, the controller 16 also includes an interactive userinterface 42, which allows the operator to view and comprehendinformation regarding the operation of the system 10. In the illustratedembodiment, the interface 42 is implemented on an interface screencarried in the lid 40, which displays information for viewing by theoperator in alpha-numeric format and as graphical images.

[0049] Further details of the controller 16 can be found in Nayak et al,U.S. Pat. No. 6,261,065, which is incorporated herein by reference.Further details of the interface can be found in Lyle et al, U.S. Pat.No. 5,581,687, which is also incorporated herein by reference.

[0050] As FIG. 1 shows, the lid 40 can be used to support otherinput/outputs to couple other external devices to the controller 16 orother components of the device 14. For example, an ethernet port 50, oran input 52 for a bar code reader or the like (for scanning informationinto the controller 16), or a diagnostic port 54, or a port 56 to becoupled to a pressure cuff 60 worn by a donor to enhance blood flowrates during blood processing (see, e.g., FIGS. 23 and 24), or a systemtransducer calibration port 58, can all be conveniently mounted foraccess on the exterior of the lid 40, or elsewhere on the case 36 of thedevice 14.

B. The Flow Set

[0051] The flow set 12, is intended to be a sterile, single use,disposable item. Before beginning a given blood processing andcollection procedure, the operator loads various components of the flowset 12 in association with the device 14 (as FIGS. 4 and 5 show). Thecontroller 16 implements the procedure based upon preset protocols,taking into account other input from the operator. Upon completing theprocedure, the operator removes the flow set 12 from association withthe device 14. The portion of the set 12 holding the collected bloodcomponent or components are removed from the device 14 and retained forstorage, transfusion, or further processing. The remainder of the set 12is removed from the device 14 and discarded.

[0052] The flow set includes a blood processing chamber 18, a fluidactuated pump and valve cassette 28, and an array associated processingcontainers 64 and flow tubing coupled to the chamber 18 and the cassette28, as will be identified in greater detail later.

1. The Blood Processing Chamber

[0053] In the illustrated embodiment (see FIG. 5), the flow set 12includes a blood processing chamber 18 designed for use in associationwith a centrifuge. The processing device 14 includes a centrifugestation 20 (see FIGS. 2 and 3, which receives the processing chamber 18for use (see FIG. 5).

[0054] As FIGS. 2 and 3 show, the centrifuge station 20 comprises acompartment 24 formed in the base 38. The centrifuge station 20 includesa door 22. The door 22 opens (as FIGS. 3 and 5 show) to allow loading ofthe processing chamber 18 into the compartment 24. The door 22 closes(as FIGS. 2 and 6 show) to enclose the processing chamber 18 within thecompartment 24 during operation.

[0055] The centrifuge station 20 rotates the processing chamber 18. Whenrotated, the processing chamber 18 centrifugally separates whole bloodreceived from a donor into component parts, principally, red bloodcells, plasma, and intermediate layer called the buffy coat, which ispopulated by platelets and leukocytes. As will be described later, theconfiguration of the chamber 18 can vary according to the intended bloodseparation objectives.

2. The Fluid Pressure-Actuated Cassette

[0056] In the illustrated embodiment, the set 12 also includes a fluidpressure-actuated cassette 28 (see FIG. 5). The cassette 28 provides acentralized, programmable, integrated platform for all the pumping andvalving functions required for a given blood processing procedure. Inthe illustrated embodiment, the fluid pressure comprises positive andnegative pneumatic pressure, although other types of fluid pressure canbe used.

[0057] As FIG. 5 shows, the cassette 28 is mounted for use in apneumatic actuated pump and valve station 30, which is located in thelid of the 40 of the case 36. The pump and valve station 30 includes adoor 32 that is hinged to move between an opened position, exposing thepump and valve station 30 (see FIG. 3) for loading and unloading thecassette 28, and a closed position, enclosing the cassette 28 within thepump and valve station 30 for use (shown in FIG. 6). The pump and valvestation 30 includes a manifold assembly 34 (see FIG. 4) located behind avalve face gasket 318. The manifold assembly 34 applies positive andnegative pneumatic pressure to the cassette 28 through the gasket 318,when the cassette 28 is when mounted on the pump and valve station 30.The pneumatic pressures direct liquid flow through the cassette 28.

[0058] Further details of the cassette 28 and the operation of the pumpand valve station 30 will be described later. Additional details canalso be found in Nayak et al, U.S. Pat. No. 6,261,065, which has beenincorporated herein by reference.

3. Blood Processing Containers and Tubing

[0059] Referred back to FIGS. 5 and 6, the flow set 16 also includes anarray of tubes and containers in flow communication with the cassette 28and the chamber 18. The arrangement of tubes and containers can varyaccording to the processing objectives. Representative blood processingprocedures and the associated flow sets accommodating such procedureswill be described later.

[0060] An umbilicus 100 forms a part of the flow set 16. When installed,the umbilicus 100 links the rotating processing chamber 18 with thecassette 28 without need for rotating seals. The umbilicus 100 can bemade from rotational-stress-resistant plastic materials, such as Hytrel®copolyester elastomers (DuPont).

[0061] Referring now to FIG. 7, tubes 102, 104, and 106 extend from theproximal end of the umbilicus 100. The tube 102 conveys whole blood intothe processing chamber 18 for separation. The tubes 104 and 106 convey,respectively, centrifugally separated red blood cells and plasma fromthe processing chamber 18. The plasma can either be rich or poor inplatelets, depending upon the processing objectives.

[0062] As FIG. 7 shows, a fixture 108 gathers the tubes 102, 104, and106 adjacent the umbilicus 100 in a compact, organized, side-by-sidearray outside the centrifuge station 20. The fixture 108 allows thetubes 102, 104, and 106 to be placed and removed as a group inassociation with an optical sensing station 46 (see FIGS. 9, 10, and11), which is located adjacent to the centrifuge station 20 outside thechamber 18.

[0063] The optical sensing station 46 optically monitors the presence orabsence of targeted blood components (e.g., red blood cells andplatelets) in blood conveyed by the tubes 104 and 106. The sensingstation 46 provides outputs reflecting the presence or absence of suchblood components. This output is conveyed to the controller 16. Thecontroller 16 processes the output and generates signals to controlprocessing events based, in part, upon the optically sensed events.Further details of the operation of the controller to control processingevents based upon optical sensing will be described later. Additionaldetails can also be found in Nayak et al, U.S. Pat. No. 6,261,065, whichhas been incorporated herein by reference.

[0064] As shown (see FIGS. 5 and 6), the flow set 16 includes aphlebotomy needle 128, through which a donor can be coupled to thesystem 10 for blood processing. In FIGS. 5 and 6, the flow set 16 alsoincludes a blood sampling assembly 110. The blood sampling assembly 110allows for the collection of one or more samples of the donor's blood atthe commencement of a given blood processing procedure, through thephlebotomy needle 128. A conventional manual clamp 114 (e.g., a RobertsClamp) is provided to control blood flow into the sampling assembly 110.

[0065] As also shown in FIGS. 5 and 6, the flow set 16 can include anin-line injection site 112. The injection site 112 allows a technicianto introduce saline or another physiologic liquid or medication into thedonor, if necessary, using the phlebotomy needle 128, and withoutrequiring an additional needle stick.

[0066] An additional in-line manual clamp 116 is desirably includedupstream of the blood sampling assembly 110 and the injection site 112.This clamp 116 makes it possible to quickly isolate the donor from theflow set 16, if donor safety or comfort requires. Alternatively, aseparate hemostat device (not shown) can be applied for the purpose.

[0067] As FIGS. 1 and 2 also show, the device 14 can include othercomponents compactly arranged to aid blood processing. In addition tothe centrifuge station 20 and pump and valve station 30, alreadydescribed, the device includes one or more weigh stations 62 and otherforms of support for containers. The arrangement of these components onthe device 14 can, or course, vary.

[0068] In the illustrated embodiment (see FIG. 3), the weigh stations 62comprise a series of container hangers/weigh sensors arranged along thetop of the lid 40. In the illustrated embodiment, additional swing-outhangers/weigh sensors are also provided on the side of the lid 40 andthe base. In use (see FIGS. 5 and 6), containers are suspended on theweigh stations 62. As FIGS. 5 and 6 also show, pictorial icons 66applied to the lid 40 adjacent to the weigh stations 62 match pictorialicons 66 applied on the containers. By matching the icons 66, theoperator is visually guided to place the proper containers on theintended weigh stations 62.

[0069] The weigh stations 62 can also comprise molded recesses in thebase 38 to rest containers. Pictorial icons 66 on the base 38 adjacentthe stations 62 match pictorial icons 66 on the containers to guide theoperator in proper placement of containers during set up.

[0070] As blood or liquids are received into and/or dispensed from thecontainers during processing, the weigh stations 62 provide outputreflecting weight changes over time. This output is conveyed to thecontroller 16. The controller 16 processes the incremental weightchanges to derive fluid processing volumes. The controller generatessignals to control processing events based, in part, upon the derivedprocessing volumes. Further details of the operation of the controller16 to control processing events will be described later. Additionaldetails can also be found in Nayak et al, U.S. Pat. No. 6,261,065, whichhas been incorporated herein by reference.

4. Blood Processing Procedures

[0071] Under the control of the controller 16, the system 10 can beconditioned to perform different blood processing procedures. The MPUincludes an application control manager that administers the activationof a library of control applications. Each control applicationprescribes procedures for carrying out given functional tasks using thecentrifuge station 20 and the pump and valve station 30 in apredetermined way. The applications can, e.g., reside as processsoftware in EPROM's in the MPU.

[0072] As will be described later, through selective application ofpressure to the cassette 28, it is possible to use the same cassette 28to carry out different blood collection procedures.

[0073] For the sake of illustration, the implementation of two clinicalprocedures will be described: (1) a plasma collection procedure; and (2)a double unit red blood cell collection procedure. During a plasmacollection procedure, whole blood from a donor is centrifugallyprocessed to yield up to 880 ml of plasma for collection. All red bloodcells are returned to the donor. During a double unit red blood cellcollection procedure, whole blood from a donor is centrifugallyprocessed to yield up to two units (approximately 500 ml) of red bloodcells for collection. All plasma constituent is returned to the donor.

[0074] Although not described in detail, other clinical procedures canbe conducted by the system 10. For example, a plasma/red blood cellcollection procedure can be performed, during which whole blood from adonor is centrifugally processed to collect up to about 550 ml of plasmaand up to about 250 ml of red blood cells. The portion of the red bloodcells not retained for collection are periodically returned to the donorduring blood separation. Plasma collected in excess of the 550 ml targetand red blood cells collected in excess of the 250 ml target are alsoreturned to the donor at the end of the procedure. As another example,during the course of a plasma collection and/or red blood cellcollection procedure, the buffy coat interface can be removed from thechamber 18 and collected. With subsequent processing to removeleukocytes, the buffy coat serves as a source of platelets.

[0075] Further details of the various blood collection procedures thatthe system 10 can accomplish are described in U.S. Pat. No. 6,261,065,which has been incorporated herein by reference.

II. Other Technical Features of the Blood Separation Components of theSystem

[0076] The blood processing chamber 18 and the centrifuge station 20 ofthe system 10 desirably possess other technical features that supportthe implementation of diverse blood processing protocols.

A. The Blood Processing Chamber

[0077] In the illustrated embodiment (see FIGS. 7 and 8), the processingchamber 18 is preformed in a desired shape and configuration, e.g., byinjection molding, from a rigid, biocompatible plastic material, such asa non-plasticized medical grade acrilonitrile-butadiene-styrene (ABS).In this arrangement, the chamber 18 includes two principal components—abase component 200 and a lid component 202.

[0078] The base component 200 includes a center hub 204. The hub 204 issurrounded by inside and outside annular walls 206 and 208 that define acircumferential blood separation channel 210. One or more radialpassages 212 extend from the hub 204 and communicate with the channel210. Blood and other fluids are directed from the hub 204 into and outof the channel 210 through these passages 212. A molded wall 214 formsan axial boundary of the separation channel 210. The lid component 202also forms another axial boundary of the separation channel 210. Whileboth axial boundaries are shown to be generally flat (i.e., normal tothe rotational axis), it should be appreciated that the axial boundariescan be tapered, rounded, V-shape, and the like.

[0079] The underside of the base component 200 includes a shapedreceptacle 216 that receives a shaped mount 218 on the far end of theumbilicus 100. The mount 218 can be secured to the receptacle 216 invarious ways—e.g., by a tight, dry press fit or by solvent bonding or byultrasonic welding—to couple the umbilicus 100 in fluid communicationwith the channel 210. The far end of the umbilicus 100 and the basecomponent 200 rotate as a unit.

[0080] All contours, ports, channels, and walls that affect the dynamicsof the blood separation process are preformed in the base component 200in one or more injection molding operations. The contours, ports,channels, and walls that are preformed in the base component 200 canvary, according to the particular separation objectives desired.Representative examples will be described in greater detail later.

B. The Centrifuge Station

[0081] The centrifuge station 20 (see FIG. 9) includes a centrifugeassembly 68. The centrifuge assembly 68 is constructed to receive andsupport the molded processing chamber 18 and umbilicus 100 for use.

[0082] As illustrated in FIG. 9, the centrifuge assembly 68 includes aframe or yoke 70 having bottom, top, and side walls 72, 74, 76. The yoke70 spins on a bearing element 78 (FIG. 9) attached to the bottom wall72. An electric drive motor 80 is coupled to the bottom wall 72 of theyoke 70, to rotate the yoke 70 about an axis 82. In the illustratedembodiment, the axis 82 is essentially horizontal (see FIG. 3), althoughother angular orientations can be used. The motor 80 is capable ofrotating the yoke 70 in either clockwise or counterclockwise directions,depending upon commands issued by the controller 16.

[0083] A carrier or rotor plate 84 spins within the yoke 70 about itsown bearing element 86, which is attached to the top wall 74 of the yoke70. The rotor plate 84 spins about an axis that is generally alignedwith the axis of rotation 82 of the yoke 70.

[0084] As FIG. 7 shows, the top of the processing chamber 18 includes anannular lip 220, to which the lid component 202 is secured. As FIG. 10shows, the rotor plate 84 includes a latching assembly 88 that removablygrips the lip 220, to secure the processing chamber 18 on the rotorplate 84 for rotation.

[0085] Details of the latching assembly 88 can be found in co-pendingU.S. patent application Ser. No. 09/976,829, filed Oct. 13, 2001 andentitled “Blood Separation Systems and Methods with Quick Attachment ofa Blood Separation Chamber to a Centrifuge Rotor,” which has beenincorporated herein by reference.

[0086] As FIG. 10 best shows, a sheath 144 on the near end of theumbilicus 100 fits into a preformed, recessed pocket 90 in thecentrifuge station 20. The pocket 90 holds the near end of the umbilicus100 in a non-rotating stationary position aligned with the mutuallyaligned rotational axes 82 of the yoke 70 and rotor plate 84.

[0087] The preformed pocket 90 is also shaped to accommodate loading ofthe fixture 108 at the same time the umbilicus sheath 144 is inserted.The tubes 102, 104, and 106 are thereby placed and removed as a group inassociation with the sensing station 46, which is also located withinthe pocket 90, as FIG. 11 shows.

[0088] Umbilicus drive or support members 92 and 94 (see FIGS. 9 and 10)are carried by a side wall 76 of the yoke 70. When the rotor plate 84 islocated in a prescribed rotational position, the support members 92 and94 are presented on the left side of the processing chamber 18 toreceive the umbilicus 100 at the same time that the sheath 144 andfixture 108 are manipulated for fitting into the pocket 90.

[0089] As FIG. 10 shows, one member 92 receives the mid portion of theumbilicus 100. The member 92 includes a surface against which the midportion of the umbilicus 100 rests. The surface forms a channel 96,which faces generally toward the yoke 70. The channel 96 accommodatespassage of the mid portion of the umbilicus 100, directing the upperportion of the umbilicus toward the other member 94. The channel 96inhibits travel of the mid portion of the umbilicus 100 in radialdirections toward and away from the rotational axis 82. However, thechannel 96 permits rotation or twisting of the umbilicus 100 about itsown axis. Before use, the surface of the channel 96 is generally convex.The convex configuration is intended to be sacrificial, in that thematerial of the convex surface is intended to be worn away during use byrotational contact with the umbilicus 100. The convex configuration isdynamically changed by contact with the umbilicus during use, to form anfinal contact configuration that is dictated by the mechanical andfrictional interaction between the channel 96 and the umbilicus 100during use.

[0090] The other member 94 receives the upper portion of the umbilicus100, which the member 92 directs toward it. The member 94 includes asurface against which the upper portion of the umbilicus 100 rests. Thesurface forms a channel 98 inclined toward the top wall 72 of the yoke70. The channel 98 generally faces away from the yoke 70, and is therebyin a reverse facing relationship with the channel 96. To provide atransitional path for the umbilicus between the two oppositely facingchannels 96 and 98, the channel 96 is offset slightly outward from thechannel 98. The channel 98 guides the upper portion of the umbilicus 100toward the recessed pocket 90, which is located axially above the topwall 72 of the yoke 70, where the umbilicus sheath 144 and fixture 108are fitted. Like the channel 96, the channel 98 inhibits travel of theupper portion of the umbilicus 100 in radial directions toward and awayfrom the rotational axis 82. However, like the channel 96, the channel98 permits rotation or twisting of the umbilicus 100 about its own axis.

[0091] Because the support channels 96 and 98 are arranged in a reversefacing relationship, the channels 96 and 98 mutually engage the midregion of the umbilicus in a complementary, “reverse grip” fashionregardless of the direction of rotation of the yoke 70.

[0092] The inward facing orientation of the channel 96 best captures theumbilicus during rotation of the yoke 70 in the counterclockwisedirection (when viewed from the top of the rotor plate 84). This, inturn, stabilizes the remainder of the umbilicus for engagement with thechannel 98 during rotation in this direction. The processing chamber 18is intended, during blood processing operations, to be rotated in acounterclockwise direction.

[0093] The member 94 includes opposed side edges 99 and 101 that taperinward toward the outward facing channel 98. The tapered side edge 101further guides the mid region of the umbilicus into engagement with theoutward facing channel 98 in response to rotation of the yoke 70 in thecounterclockwise direction.

[0094] The outward facing guide edge 99 of the channel 98 defines anenlarged curved surface or ramp that extends toward the rotational axis82. The ramp 99 is sized and configured to accomplish self-loading theumbilicus into the channel 98 when the yoke is rotated in this clockwisedirection (as viewed from the top of the rotor plate 84), which is thedirection opposite to the direction of rotation intended for regularblood processing (i.e., counterclockwise). The ramp 99 also thereafterkeeps the upper portion of the umbilicus 100 from slipping out of thechannel 98 when the yoke 70 is rotated in a counterclockwise direction.This, in turn, stabilizes the remainder of the umbilicus for engagementwith the channel 96 during rotation in this direction.

[0095] The configurations of the channels 96 and 98 thereby complementeach other, to keep the mid region of the umbilicus in engagement withthe channels 96 and 98 in response to rotation of the yoke 70 andregardless of the direction of rotation of the yoke 70.

[0096] In the illustrated embodiment, the channel surfaces 96 and 98 ofthe support members 92 and 94 are preferably fabricated from a lowfriction material, to thereby eliminate the need for externallubrication or rotating bearings on the umbilicus 100 itself. Thematerial used can, e.g., comprise Teflon® polytetrafluoroethylenematerial (DuPont) or an ultra high molecular weight polyethylene. Madefrom such materials, the channel surfaces 96 and 98 minimize umbilicusdrive friction and the presence of particulate matter due to umbilicuswear.

[0097] Further details of the support members 92 and 94 can be found inco-pending U.S. patent application Ser. No. 09/976,830, filed Oct. 13,2001, and entitled “Blood Separation Systems and Methods with UmbilicusDriven Blood Separation Chambers,” which is incorporated herein byreference.

[0098] Closing the centrifuge station door 20 positions a holdingbracket 21 on the underside of the door 20 (see FIG. 5) in registry withthe sheath 144. Another holding bracket 23 (as shown in FIG. 5) on theunderside of the door 20 is positioned in registry with the fixture 108when the door 20 is closed. A releasable latch 25 preferably holds thedoor 20 shut during operation of the centrifuge assembly 68 (as FIG. 6shows).

[0099] During operation of the centrifuge assembly 68, the supportmembers 92 and 94 carry the umbilicus 100 so that rotation of the yoke70 also rotates the umbilicus 100 in tandem about the axis 82.Constrained within the pocket 90 at its near end (i.e., at the sheath144) and coupled to the chamber 16 at its far end (i.e., by the mount218), the umbilicus 100 twists upon the channel surfaces 96 and 98 aboutits own axis as it rotates about the axis 82, even as the channelsurfaces 96 and 98 inhibit radial travel of the umbilicus relative tothe rotation axis 82. The twirling of the umbilicus 100 about its axisas it rotates upon the channel surfaces 96 and 98 at one omega with theyoke 70 (typically at a speed of about 2250 RPM) imparts a two omegarotation to the processing chamber 18 secured for rotation on the rotorplate 84.

[0100] The relative rotation of the yoke 70 at a one omega rotationalspeed and the rotor plate 84 at a two omega rotational speed, keeps theumbilicus 100 untwisted, avoiding the need for rotating seals. Theillustrated arrangement also allows a single drive motor 80 to impartrotation, through the umbilicus 100, to the mutually rotating yoke 70and processing chamber 18 carried on the rotor plate 84. Further detailsof this arrangement are disclosed in Brown et al U.S. Pat. No.4,120,449, which is incorporated herein by reference.

[0101] As before described, the channel surfaces 96 and 98 re desirablyformed and oriented in a complementary fashion to accommodate rotationof the umbilicus 100 and the driving of the processing chamber 18 ineither clockwise or counter clockwise directions. Thus, the chamber 18can be rotated in one direction conducive to one desired processingobjective, e.g., to accommodate priming and air venting prior to bloodprocessing, and be rotated in an opposite direction conducive to adifferent processing objective, e.g., blood separation. Furthermore, theclose juxtaposition of the umbilicus supports 92 and 94 to the umbilicus100 when the rotor plate 84 is in the prescribed rotational position toaccommodate mounting of the processing chamber 18, and the complementaryorientations of the channels 96 and 98 formed in the supports 92 and 94,which lead the near end of the umbilicus toward the support pocket 90,make possible an “easy-load” sequence of intuitive steps, largelycapable of being carried out in tandem, for loading the processingchamber 18 for use and unloading the processing chamber 18 after use.The contours and orientations of the channels 96 and 98 aid in“capturing” the umbilicus 100 as a result of rotation of the yoke 70 ineither direction, to thereby properly orient the umbilicus 100 on thechannel surfaces 96 and 98, even should the operator fail to load theumbilicus 100 entirely correctly in the first instance.

[0102] More particularly, the complementary features of the channels 96and 98 can be advantageously used to self-load the umbilicus 100 foruse. Desirably, once the processing chamber 18 is loaded onto the rotorplate 84, and the umbilicus sheath 144 has been placed into the pocket90, while also initially placing the mid region of the umbilicus 100into the channels 96 and 98, the yoke 70 can then be initially rotatedat a moderate speed (e.g., 300 RPM) in the clockwise direction, which isthe direction in which the yoke 70 is rotated during blood processingoperations. Rotation in this direction makes use of the elongated ramp99 to assure that the umbilicus 100 is fully loaded into the channel 98.Thereafter, the yoke 70 can be rotated at the moderate speed in theopposite (counterclockwise) direction, to assure that the position ofthe umbilicus 100 has been stabilized in both channels 96 and 98 foruse. The yoke 70 can then be fully ramped up to a rotational speed inthe counterclockwise direction conducive for blood processing.

C. Interface Control by Optical Sensing

[0103] In any of the above-described blood processing procedures, thecentrifugal forces present within the processing chamber 18 separatewhole blood into a region of packed red blood cells and a region ofplasma (as diagrammatically shown in FIG. 12. The centrifugal forcescause the region of packed red blood cells to congregate along theoutside or high-G wall of the chamber, while the region of plasma istransported to the inside or low-G wall of the chamber.

[0104] An intermediate region forms an interface between the red bloodcell region and the plasma region. Intermediate density cellular bloodspecies like platelets and leukocytes populate the interface, arrangedaccording to density, with the platelets closer to the plasma layer thanthe leukocytes. The interface is also called the “buffy coat,” becauseof its cloudy color, compared to the straw color of the plasma regionand the red color of the red blood cell region.

[0105] It is desirable to monitor the location of the buffy coat, eitherto keep the buffy coat materials out of the plasma or out of the redblood cells, depending on the procedure, or to collect the cellularcontents of the buffy coat. The system includes the optical sensingstation 46 (also shown in FIGS. 11A to 11D), which houses two opticalsensing assemblies 146 and 148 for this purpose. This arrangement isalso diagrammatically shown in FIGS. 12, 13, and 14.

[0106] The first sensing assembly 146 in the station 46 opticallymonitors the passage of blood components through the plasma collectiontube 106. The second sensing assembly 148 in the station 46 opticallymonitors the passage of blood components through the red blood cellcollection tube 104.

[0107] The tubes 104 and 106 are made from plastic (e.g.polyvinylchloride) material that is transparent to the optical energyused for sensing, at least in the region where the tubes 104 and 106 areto be placed into association with the sensing station 46. The fixture108 holds the tubes 104 and 106 in viewing alignment with its respectivesensing assembly 148 and 146. The fixture 108 also holds the tube 102,which conveys whole blood into the centrifuge station 20, even though noassociated sensor is provided. The fixture 108 serves to gather and holdall tubes 102, 104, and 106 that are coupled to the umbilicus 100 in acompact and easily handled bundle.

[0108] The first sensing assembly 146 is capable of detecting thepresence of optically targeted cellular species or components in theplasma collection tube 106. The components that are optically targetedfor detection vary depending upon the procedure.

[0109] For a plasma collection procedure, the first sensing assembly 146detects the presence of platelets in the plasma collection tube 106, sothat control measures can be initiated to move the interface between theplasma and platelet cell layer back into the processing chamber. Thisprovides a plasma product that can be essentially platelet-free or atleast in which the number of platelets is significantly minimized.

[0110] For a red blood cell-only collection procedure, the first sensingassembly 146 detects the interface between the buffy coat and the redblood cell layer, so that control measures can be initiated to move thisinterface back into the processing chamber. This maximizes the red bloodcell yield.

[0111] The presence of these cellular components in the plasma, asdetected by the first sensing assembly 146, indicates that the interfaceis close enough to the low-G wall of the processing chamber to allow allor some of these components to be swept into the plasma collection line(see FIG. 13). This condition will also be called an “over spill.”

[0112] The second sensing assembly 148 is capable of detecting thehematocrit of the red blood cells in the red blood cell collection tube104. The decrease of red blood hematocrit below a set minimum levelduring processing that the interface is close enough to the high-G wallof the processing chamber to allow plasma to enter the red blood cellcollection tube 104 (see FIG. 14). This condition will also be called an“under spill.”

[0113] The construction of the sensing station 46 and the first andsecond sensing assemblies 146 and 148 can vary. In a desiredimplementation, the first sensing assembly 146 includes a light emittingdiode (LED) 400 that can selectively emit either red or green light, andan oppositely facing photodiode 402, for measuring intensity of lighttransmitted through the plasma tube 106 by the LED 400. The differentwavelengths (green and red) of the LED 400 are selected to havegenerally the same attenuation for platelets but significantly differentattenuation for red blood cells. The first sensing assembly 146 canthereby differentiate between the presence of platelets in the plasmaflow (to detect an over spill during a plasma collection procedure) andthe presence of red blood cells in the plasma flow (to detect the buffycoat interface with red blood cells during a buffy coat collectionprocedure).

[0114] In a desired implementation, the second sensing assembly 148includes an infrared LED 404 and two photodiodes 406 and 408, one 406adjacent the infrared LED 404 and the other 408 facing opposite to theinfrared LED 404. The photodiode 408 measures light intensitytransmitted through the red blood cell tube 104 by the LED 404. Thephotodiode 406 measures reflected light intensity.

[0115] The sensing station 46 and the fixture 108 locate the red bloodcell tube 104 in a desired distance relationship to the infrared LED 404and photodiode 406, which has been observed to result in a linearcorrelation between measured reflected light intensity and red bloodcell hematocrit. As an example, the intensity of reflected lightmeasured at a predetermined radial distance (e.g., 7.5 mm) from anincident light source having a wavelength in the NIR spectrum (e.g., 805nm) (i.e., LED 404) varies as a linear function with hematocrit for ahematocrit range of at least 10 and 90. Thus, red blood cell hematocritcan be ascertained by monitored reflected light intensity using theinfrared LED 404 and the photodiode 406.

[0116] The sensing station 46 can be constructed in various ways. In oneimplementation, shown in FIGS. 11A to 11D, the station 46 includes amolded body 500 comprising two facing plates 502 and 504. The plates 502and 504 are spaced apart to receive the fixture 108 and to hold the redblood cell tube 104 and plasma tube 106 in precise alignment with thefirst and second sensing assemblies 146 and 148.

[0117] Each plate 502 and 504 includes an array of light pipes 506 A/B/Cand 508 A/B/C that desirably comprise integrally molded components ofthe body 500. The light pipes 506 A/B/C and 508 A/B/C are in preciseoptical alignment with the LED's and photodiodes comprising the firstand second sensing assemblies 146 and 148. These LED's and photodiodesare carried on circuit boards 510 that are mounted on the exterior ofthe body 500 facing the light pipes, e.g., using fasteners.

[0118] More particularly, the light pipe 506A of the plate 502 is inoptical alignment with the photodiode 402 of the first sensing assembly146. Correspondingly, the oppositely facing light pipe 508A of the plate504 is in optical alignment with the red/green LED 400 of the firstsensing assembly 146.

[0119] The light pipe 506B of the plate 502 is in optical alignment withthe infrared LED 404 of the second sensing assembly 148.Correspondingly, the oppositely facing light pipe 508B of the plate 504is in optical alignment with the transmitted light-detecting photodiode408 of the second sensing assembly 148. The light pipe 506C of the plate502 is in optical alignment with the reflected light-detectingphotodiode 406 of the second sensing assembly 148. In this arrangement,the light pipe 508C of the plate 504 is empty.

[0120] The control circuitry supporting the first and second sensingassemblies 146 and 148 can also vary. In a representative embodiment,(schematically shown in FIGS. 11E and 11F), a CPLD controller 410 (seeFIG. 11F) receives a serial data stream (data stream B in FIGS. 11E and11F) from a selected one of the photodiodes 402, 406, and 408, which isindicative a sensed light intensity (transmitted or reflected, as thecase may be) sensed by the selected photodiode. The CPLD controller 410generates a photodiode selection signal (selection signal C in FIGS. 11Eand 11F) to select the photodiode 402, 406, or 408) for data streamreceipt.

[0121] The CPLD controller 410 controls the gain of gain amplifiers 412individually associated with each photodiode 402, 406, and 408 (see FIG.11E), via a digital data stream (data stream C in FIGS. 11E and 11F),which is generated by a serial output port contained within thecontroller 410. Each gain amplifier 412 receives a voltage signal from acurrent-to-voltage converter 414 individually associated with eachphotodiode 402, 406, 408, which converts the current output of eachphotodiode 404, 406, and 408 to a voltage.

[0122] The amplified analog voltage output of each gain amplifier 412 isapplied to individual analog-to-digital converters, which converts theanalog voltage into the serial data stream for the selected photodiode(data stream B), which the CPLD controller 410 receives for furtherprocessing.

[0123] The serial data stream B received by the CPDL controller 410 isapplied to a serial to parallel port 418 to create a parallel datastream. The original analog voltage from the selected gain amplifier 412is reconstructed by a digital to analog converter 420 and applied to abandpass filter 422. The bandpass filter 422 has a center frequency atthe carrier frequency of the modulated source light (i.e., 2 KHz in theillustrated embodiment) . The output of the bandpass filter 422 (whichis sinusoidal) is sent to a full wave rectifier, which transforms thesinusoidal output to a DC output voltage proportional to the sensedlight intensity.

[0124] A current source 428 is coupled to the LED's 400 and 404. Thecurrent source 428 uniformly supplies current to each LED 400 and 404,independent of temperature and the power supply voltage levels. Amodulator 430 modulates the constant current at a prescribed frequency.The modulation 430 removes the effects of ambient light andelectromagnetic interference (EMI) from the optically sensed reading. Incombination with the uniform current source 428, the CPLD controller 410also adjusts the magnitude of uniform current, and therefore theintensity of each LED 400 and 404. LED current control data is generatedin serial form by the controller 410 (serial data stream A in FIGS. 11Eand 11F). This serial data is applied to digital-to-analog converters426, individually associated with each current source 428 for each LED400 and 404.

[0125] The sensing assemblies 146 and 148 are operated by the controller16, which periodically actuates the sensing assemblies 146 and 148 andsamples the sensed intensity outputs. Desirably, a given sensor outputused for control purposes comprises an average of multiple samples takenduring a prescribed sampling period. For example, during a givensampling period (e.g., every 100 μsec), multiple samples (e.g., 64) aretaken. An average of these multiple samples is derived. The variance ofthe sample average is also desirably determined by conventionalmethodologies, and the sample average is validated if the variance isless than a prescribed maximum. If the variance of the sample average isequal to or greater than the prescribed maximum, the sample average isnot used for control purposes. Desirably, to provide a more dependableoutput, a running average of the last five validated sample averages isused as the control value. As will be described in greater detail later,the magnitude of the sample variance can also be used as a means fordetecting the presence of air bubbles during an air purge conducted atthe end of a given blood processing procedure.

[0126] Further details of optical sensing arrangements are disclosed inU.S. Pat. No. 6,261,065, which has been incorporated herein byreference.

III. Technical Features of the Pneumatically Actuated Flow ControlComponents of the System

[0127] The cassette 28 and the pump and valve station 30 of the system10 desirably also possess other technical features that support diverseblood processing protocols.

A. The Cassette

[0128] In a preferred embodiment (see FIG. 15), the cassette 28comprises an injection molded body 300 made of a rigid medical gradeplastic material. Flexible diaphragms 302 and 304, preferably made offlexible sheets of medical grade plastic, overlay, respectively, thefront side and back sides of the cassette 28. The diaphragms 302 and 304are sealed about their peripheries to the peripheral edges of the frontand back sides of the cassette 28.

[0129] As FIG. 15 shows, the cassette 28 has an array of interiorcavities formed on both the front and back sides. The interior cavitiesdefine pneumatic pump stations (schematically designated PS in FIG. 15),which are interconnected by a pattern of fluid flow paths (schematicallydesignated FP in FIG. 15) through an array of in line, pneumatic valvestations (schematically designated VS in FIG. 15).

[0130] The layout of the interior cavities can vary according to thedifferent objectives of different blood processing procedures.Desirably, the interior cavities of the cassette 28 define aprogrammable blood processing circuit 306 (see FIGS. 16 and 17). Theprogrammable circuit 306 can be conditioned by the controller 16 toperform a variety of different blood processing procedures in which,e.g., red blood cells are collected, or plasma is collected, or bothplasma and red blood cells are collected, or the buffy coat iscollected.

[0131]FIG. 16 diagrammatically shows a programmable fluid circuit 306that can be implemented as an injection molded, pneumatically controlledcassette 28 of the type shown in FIG. 15. FIG. 17 shows the specificimplementation of the fluid circuit 306 in the cassette body 300. Aswill be described, the cassette 28 interacts with the pneumatic pump andvalve station 30 to provide a centralized, programmable, integratedplatform, capable of performing different blood processing functions.

[0132] The fluid circuit 306 includes dual pneumatic pump chambers DP1and DP2 (see FIGS. 16 and 23) . The pump chambers DP1 and DP2 aredesirably operated by the controller 16 in tandem to serve as a generalpurpose, donor interface pump. The dual donor interface pump chambersDP1 and DP2 work in parallel. One pump chamber draws fluid, while theother pump chamber expels fluid. The dual pump chambers DP1 and DP2thereby alternate draw and expel functions to provide a uniform outletflow. The donor tube 126 having the attached phlebotomy needle 128 iscoupled to pump chambers DP1 and DP2.

[0133] The fluid circuit 306 also desirably includes a pneumatic pumpchamber ACP, which serves as a dedicated anticoagulant pump, to drawanticoagulant from an external container 150 and meter the anticoagulantinto the blood drawn from the donor through an anticoagulant tube 152,which is coupled to the donor tube 126.

[0134] A donor clamp 154 external to the fluid circuit 306 (see alsoFIGS. 4 and 5) is operated by the controller 16 to close the donor tube126 and anticoagulant tube 152 when specified conditions occur duringblood processing that could affects the comfort or safety of the donor.The donor clamp 154 serves to isolate the donor from the fluid circuit306 when these conditions occur. The manually operated clamp 116 or ahemostat is also desirably placed downstream of the donortube-anticoagulant tube 152 junction for added donor safety.

[0135] The fluid circuit 306 shown in FIG. 16 also desirably includes apneumatic pump chamber IPP that serves as a dedicated in-process wholeblood pump, to convey whole blood from a reservoir 158 into theprocessing chamber 18. The dedicated function of the pump chamber IPPfrees the donor interface pump chambers DP1 and DP2 from the addedfunction of supplying whole blood to the processing chamber 18. Thus,the in-process whole blood pump chamber IPP can maintain a continuoussupply of blood to the processing chamber 18, while the donor interfacepump chambers DP1 and DP2 operate in tandem to simultaneously draw andreturn blood to the donor through the single phlebotomy needle.Processing time is thereby minimized.

[0136] The fluid circuit 306 also desirably includes a pneumatic pumpchamber PP that serves as a plasma pump, to convey plasma from theprocessing chamber 18 into a collection container 160. The ability todedicate separate pumping functions provides a continuous flow of bloodinto and out of the processing chamber 18, as well as to and from thedonor.

[0137] The fluid circuit 306 includes an array of valves, designated V1to V26 in FIG. 16, that connect the pump chambers DP1; DP2, IPP, PP, andACP to an array of flow paths that transport blood and blood componentsto and from the donor and to and from the processing chamber. Thefunctions of the valves V1 to V26 are summarized in the following table:Valve Valve Function V1 Controls fluid flow through flow port 0 of IPPV2 Controls isolation of an external collection container 162 intendedto collect red blood cells during processing V3 Controls conveyance ofred blood cells to the external collection container 162 V4 Controlsconveyance of whole blood to the external in process container 158 V5Controls conveyance of red blood cells for return to the donor throughthe donor tube 126 V6 Controls fluid conveyance through one an end ofDP1 V7 Controls fluid conveyance through an end of DP2 V8 Controlsconveyance of processing solution (e.g., saline) through ends of DP1 andDP2 from an external solution container 162 V9 Controls isolation of theexternal collection container 160 intended to collect plasma duringprocessing V10 Controls conveyance of plasma for return to the donorthrough the donor tube 126 V11 Controls fluid conveyance through an endof PP V12 Control fluid conveyance to and from donor tube 126 V13Controls fluid conveyance through an end of DP1 V14 Controls fluidconveyance through an end of DP2 V15 Controls conveyance of processingsolution (e.g., saline) through ends of DP1 and DP2 from the externalsolution container 164 V16 Controls fluid conveyance through an end ofIPP V17 Controls fluid conveyance through an end of PP V18 Controlsfluid conveyance through a chamber housing a filtration medium, intendedto filter blood being returned to the donor through the donor tube 126V19 Controls isolation of an external collection container 166 intendedto collect buffy coat during processing (if called for by the bloodprocessing protocol) V20 Controls isolation of the external container164 holding processing fluid V21 Controls fluid conveyance of red bloodcells through tube 104 from the processing chamber. V22 Controls fluidconveyance through an end of ACP V23 Controls fluid conveyance throughand end of ACP V24 Controls isolation of an external container 168 thatholds a blood additive solution (if called for by the blood processingprotocol) V25 Controls isolation of the external container 164 holdingprocessing fluid V26 Controls fluid conveyance to addition externalblood collection container(s) 172 (if called for by the blood processingprotocol)

[0138] The flexible diaphragms 302 and 304 overlaying the front and backsides of the cassette body 300 rest against upstanding peripheral edgessurrounding the pump chambers DP1, DP2, IPP, PP, and ACP; the valves V1to V26, and array of connecting flow paths. The pre-molded ports P1 toP13 (see FIGS. 16 and 17) extend out along two side edges of thecassette body 300 to couple the fluid circuit 306 within the cassettebody 300 to already described external containers and to the donor.

[0139] The cassette 28 is vertically mounted for use in the pump andvalve station 30, as shown in FIG. 5. In this orientation (see FIG. 15as well), the diaphragm 302 faces outward toward the door 32 of thevalve station 30, ports P8 to P13 face downward, and the ports P1 to P7are vertically stacked one above the other and face inward.

[0140] As will be described, localized application by the pump and valvestation 30 of positive and negative fluid pressures upon the backsidediaphragm 304 serves to flex the diaphragm 304 to close and open thevalve stations V1 to V26 and/or to expel and draw liquid out of the pumpchambers DP1, DP2, IPP, PP, and ACP.

[0141] As set forth in the above table, an additional interior cavity308 is provided in the cassette body 300. The cavity 308 forms a stationthat holds a blood filter material 174 (see FIG. 17) to remove clots andcellular aggregations that can form during blood processing. As shownschematically in FIG. 16, the cavity 308 is placed in the circuit 306between the port P8 and the donor interface pump stations DP1 and DP2,so that blood returned to the donor passes through the filter 174. Thecavity 308 also serves to trap air in the flow path to and from thedonor.

[0142] Another interior cavity 310 (see FIG. 16) is also provided in thecassette body 300. The cavity 310 is placed in the circuit 306 betweenthe port P5 and the valve V16 of the in-process pumping station IPP. Thecavity 310 serves as another air trap within the cassette body 300 inthe whole blood flow path serving the separation chamber 18. The cavity310 also serves as a capacitor to dampen the pulsatile pump strokes ofthe in-process pump IPP serving the separation chamber 18.

B. Pump and Valve Station

[0143] The cassette 28 interacts with a pneumatic actuated pump andvalve station 30, which is mounted in the lid of the 40 of the case 36(see FIG. 15).

[0144] The inside face 324 of the door 32 of the pump and valve station30 (which is desirably metal, as will be explained later) carries anelastomeric gasket 312. The gasket 312 contacts the front side of thecassette body 300 when the door 32 is closed. An inflatable bladder 314lays between the gasket 312 and the inside face 324 of the door. Withthe door 32 opened (see FIG. 3), the operator can place the cassette 28into the pump and valve station 30. Closing the door 32 and securing thelatch 316 (shown in FIGS. 3 to 5) brings the gasket 312 into facingcontact with the diaphragm 302 on the front side of the cassette body300. Inflating the bladder 314 presses the gasket 312 into intimate,sealing engagement against the diaphragm 302. The cassette body 300 isthereby secured in a tight, sealing fit within the pump and valvestation 30.

[0145] The pump and valve station 30 includes a pneumatic manifoldassembly 34, which is best shown in FIG. 15. In use, the diaphragm 304is held by the bladder 314 in intimate engagement against the manifoldassembly 34 when the door 32 of the pump station 20 is closed and thebladder 314 is inflated. Desirably, a valve face gasket 318 overlies thepneumatic manifold assembly 34, to serve as a spill shield. FIG. 3 showsthe presence of the valve face gasket 318, while, in FIGS. 4 and 15, thevalve face gasket 318 has been partially removed to better show themanifold assembly 34.

[0146] The manifold assembly 34 includes an array of actuator ports 320arranged to mirror the array of pump chambers and valves on the cassette28. Under the control of the controller 16, the manifold assembly 34selectively distributes the different pressure and vacuum levels to theactuator ports 320, which apply the levels of pressure and vacuumsystematically to the pump chambers and valve of the cassette 28 throughthe diaphragm 304, to route blood and processing liquids in an intendedfashion through the fluid circuit 306. Under the control of thecontroller 16, the manifold assembly 34 also distributes pressure levelsto the door bladder 314 (already described), as well as to the donorpressure cuff 60 (see FIG. 23) and to the donor clamp 154 (alreadydescribed).

[0147] The manifold assembly 34 generates Phard, or Hard Pressure, andPinpr, or In-Process Pressure, which are high positive pressures (e.g.,+500 mmHg) applied for closing the cassette valves V1 to V26 and todrive the expression of liquid from the in-process pump IPP and theplasma pump PP. The magnitude of Pinpr is sufficient to overcome aminimum pressure of approximately 300 mm Hg, which is typically presentwithin the processing chamber 18. Pinpr and Phard are operated at thehighest pressure to ensure that upstream and downstream valves used inconjunction with pumping are not forced opened by the pressures appliedto operate the pumps.

[0148] The manifold assembly 34 also generates Pgen, or General Pressure(+300 mmHg), which is applied to drive the expression of liquid from thedonor interface pumps DP1 and DP2 and the anticoagulant pump ACP.

[0149] The manifold assembly 34 also generates Vhard, or Hard Vacuum(−350 mmHg), which is the deepest vacuum applied in the manifoldassembly 34 to open cassette valves V1 to V26. The manifold assembly 34also generates Vgen, or General Vacuum (−300 mmHg), which is applied todrive the draw function of each of the pumps DP1, DP2, IPP, PP, and ACP.Vgen is required to be less extreme than Vhard, to ensure that pumpsDP1, DP2, IPP, PP, and ACP do not overwhelm upstream and downstreamcassette valves V1 to V26.

[0150] Further details of the operation of the pump and valve station 30can be found in U.S. Pat. No. 6,261,065, which has been incorporatedherein by reference.

C. Capacitive Flow Sensing

[0151] The controller 16 desirably includes means for monitoring fluidflow through the pump chambers of the cassette 28. In the illustratedembodiment, the pump and valve station 30 carries small printed circuitboard assemblies (PCBA's) 332. One PCBA 332 is associated with eachpneumatic actuator port 320 that applies negative and positive pressureto the diaphragm 304 to draw fluid into and expel fluid from thecassette pump chambers DP1; DP2; IPP; PP; and ACP. The PCBA's 332 areeach coupled to an electrical source and are each part of a capacitivecircuit that is in electrical conductive interaction or contact withfluids within their respective pump chambers. The capacitive circuitscomprise capacitors sandwiching each pump chamber. Each PCBA 332 formsone capacitor plate, and the metallic inside face 324 of the door 32 ofthe pump and valve station 30 forms the other capacitor plate. Betweenthe plates are the pump chambers themselves. Fluid in the pump chambersare shielded from actual physical contact with the circuits by virtue ofthe cassette diaphragms 302 and 304, the valve face gasket 318 overlyingthe pneumatic manifold assembly 34, and the gasket 312 overlying theinside face 324 of the door 32. The passage of electrical energy througheach PCBA 332 creates an electrical field within the respective pumpchamber. Cyclic deflection of the diaphragm 304 associated with a givenpump chamber to draw fluid into and expel fluid from the pump chamberchanges the electrical field, resulting in a change in total capacitanceof the circuit through the PCBA 332. Capacitance increases as fluid isdraw into the pump chamber, and capacitance decreases as fluid isexpelled from pump chamber.

[0152] In this arrangement, the PCBA's 332 each includes a capacitivesensor (e.g., a Qprox E2S). The capacitive sensor registers changes incapacitance for the circuit 332 for each pump chamber. The capacitancesignal for a given circuit 332 has a high signal magnitude when the pumpchamber is filled with liquid, has a low signal magnitude signal whenthe pump chamber is empty of fluid, and has a range of intermediatesignal magnitudes when the diaphragm occupies intermediate positions.

[0153] At the outset of a blood processing procedure, the controller 16can calibrate the difference between the high and low signal magnitudesfor each sensor to the maximum stroke volume of the respective pumpchamber. The controller 16 can then relate the difference between sensedmaximum and minimum signal values during subsequent draw and expelcycles to fluid volume drawn and expelled through the pump chamber. Thecontroller 16 can sum the fluid volumes pumped over a sample time periodto yield an actual flow rate.

[0154] The controller 16 can compare the actual flow rate to a desiredflow rate. If a deviance exists, the controller 16 can vary pneumaticpressure pulses delivered to the actuators for the cassette pumpchambers to minimize the deviance.

[0155]FIG. 15 shows the PCBA's 332 located entirely outside the cassette28, being face-mounted within the associated actuator port 320. In onealternative embodiment, a component of the circuit 332 (e.g., one of thecapacitor plates) can be placed inside the pump chamber of the cassette28, with the electrical connection to the rest of the circuit routedoutside the pump chamber. In another alternative embodiment, the circuit332 and electrical connections can be implemented on flexible electrodecircuits face-mounted on the manifold assembly 34 or as molded circuitboard components integrated with the body of the manifold assembly 34.In the latter embodiment, electrical circuitry or routing is molded onthermoplastic parts, e.g., by lithographic patterning, over-molding, orby sealing a flexible circuit to a component part. The thermoplasticparts, which perform electrical functions, are integrated, e.g., byultrasonic welding, to other components that perform the pneumaticfunctions of the manifold assembly 34, forming compact, multi-layer,multi-functional assemblies. In this arrangement, electrical connectionwith the external controller 16 and other external sensors can beachieved, e.g., by female electrical connectors soldered into place toreceive electrical pins from the controller 16 and related sensors,and/or by use of consolidated ribbon cables.

IV. Use of System to Perform a Plasma Collection Procedure

[0156] Use of a blood flow set 12 in association with the device 14 andcontroller 16 to conduct a typical plasma collection procedure will nowbe described.

[0157] The plasma collection procedure includes a pre-collection cycle,a collection cycle, and a post-collection cycle. During thepre-collection cycle, the flow set 16 is primed with saline to vent airprior to venipuncture. During the collection cycle, whole blood drawnfrom the donor is processed to collect plasma, while returning red bloodcells to the donor. During the post-collection cycle, excess plasma isreturned to the donor, and the set 16 is flushed with air, as will bedescribed in greater detail later.

A. The Blood Processing Chamber

[0158]FIG. 18 shows an embodiment of the centrifugal processing chamber18, which can be used in association with the system 10 shown in FIG. 1to perform a plasma collection procedure, yielding plasma that is freeor essentially free of platelets, red blood cells, and leukocytes. Thechamber 18 shown in FIG. 18 can also be used to perform a plasma/redblood cell collection procedure.

[0159] As previously described with respect to embodiment of a chambershown in FIG. 8 (with like parts being assigned like referencenumerals), the processing chamber 18 is desirably fabricated asseparately molded base component 200 and a lid component 202. The moldedhub 204 is surrounded radially by inside and outside annular walls 206and 208 that define a circumferential blood separation channel 210. Amolded wall 214 (see FIG. 19) forms an axial boundary of the channel210. The lid component 202 forms another axial boundary of the channel210. While both axial boundaries are shown to be generally flat (i.e.,normal to the rotational axis), it should be appreciated that the axialboundaries can be tapered, rounded, V-shape, and the like. Whenassembled, the lid component 202 is secured to the top of the chamber18, e.g., by use of a cylindrical sonic welding horn.

[0160] In the chamber 18 shown in FIG. 18, the inside annular wall 206is open between one pair of stiffening walls. The opposing stiffeningwalls form an open interior region 222 in the hub 204, whichcommunicates with the channel 210. Blood and fluids are introduced fromthe umbilicus 100 into and out of the separation channel 210 throughthis region 222.

[0161] In the embodiment shown in FIG. 18, a molded interior wall 224 isformed inside the region 222 that extends entirely across the channel210, joining the outside annular wall 208. The wall 224 forms a terminusin the separation channel 210, which interrupts flow circumferentiallyalong the channel 210 during separation.

[0162] Additional molded interior walls divide the region 222 into threepassages 226, 228, and 230. The passages 226, 228, and 230 extend fromthe hub 204 and communicate with the channel 210 on opposite sides ofthe terminus wall 224. Blood and other fluids are directed from the hub204 into and out of the channel 210 through these passages 226, 228, and230.

[0163] As the processing chamber 18 is rotated (arrow R in FIG. 18), anumbilicus 100 (not shown) conveys whole blood into the channel 210through the passage 226. The whole blood flows in the channel 210 in thesame direction as rotation (which is counterclockwise in FIG. 18).Alternatively, the chamber 18 can be rotated in a direction opposite tothe circumferential flow of whole blood, i.e., clockwise, although wholeblood flow is the same direction as rotation is believed desirable foroptimal blood separation.

[0164] The whole blood separates within the chamber 18 as a result ofcentrifugal forces in the manner shown in FIG. 12. Red blood cells aredriven toward the high-G wall 208, while lighter plasma constituent isdisplaced toward the low-G wall 206. The buffy coat layer residesbetween the walls 206 and 208.

[0165] Circumferentially spaced adjacent the terminus wall 224 nearly360-degrees from the whole blood inlet passage 226 are the plasmacollection passage 228 and the red blood cell collection passage 230. Inan upstream flow direction from these collection passages 228 and 230, abarrier 232 projects into the channel 210 from the high-G wall 208. Thebarrier 232 forms a constriction in the separation channel 210 along thelow-G wall 206. In the circumferential flow direction of the blood, theconstriction leads to the plasma collection passage 228.

[0166] As FIGS. 20 and 21 show, the leading edge 234 of the barrier 232is tapered toward an annular boundary of the channel 210 (which, in theillustrated embodiment, is the annular wall 214) in the direction towardthe terminus wall 224. The tapered edge 234 of the barrier 232 leads toan opening 236, which faces the annular boundary of the separationchannel 210. The opening 236 faces but is spaced axially away from theannular boundary closely adjacent to the high-G wall 208. The opening236 communicates with the red blood cell collection passage 230.

[0167] A ledge 238 extends an axial distance within the opening 236radially from the low-G wall 206. The ledge 238 constricts the radialdimension of the opening 236 along the high-G wall 208. Due to the ledge238, only red blood cells and other higher density components adjacentto the high-G wall 208 communicate with the opening 236. The ledge 238keeps plasma, which is not adjacent the high-G wall 208, away fromcommunication with the opening 236. Due to the radial restricted opening236 along the high-G wall 208, the plasma has nowhere to flow excepttoward the plasma collection passage 228. The plasma exiting theseparation channel 210 is thereby free or essentially free of the higherdensity materials, which exit the separation channel 210 through therestricted high-G opening 236.

[0168] The ledge 238 joins an axial surface 240, which is generallyaligned with the low-G wall 206. The axial surface 240 extends axiallyalong the axis of rotation to the red blood cell collection passage 230.By virtue of the barrier 232, the ledge 238, and other interior walls,the red blood cell collection passage 230 is isolated from the plasmacollection passage 228 (as FIG. 22 shows).

[0169] As FIG. 22 also best shows, plasma residing along the low-G wall206 is circumferentially directed by the barrier 232 and ledge 238 tothe plasma collection passage 228 and into the umbilicus 100. The higherdensity fluid containing red blood cells and the buffy coat components(platelets and leukocytes), which reside closer to the high-G wall 208,are directed axially along the tapered edge 234 of the barrier 232toward an annular boundary and the restricted high-G opening 236. Fromthe high-G opening 236, the red blood cells and buffy coat componentscomprising the higher density fluid are directed over the radial ledge238 toward the low-G wall 206, and then axially into the red blood cellcollection passage 230 and into the umbilicus 100.

[0170] The tapered edge 234 that leads the higher density materialsaxially toward an annular boundary of the separation channel 210 forcollection mitigates against abrupt changes in flow directions while thehigher and lower density materials are directed toward their respectivecollection passages 230 and 228. Abrupt changes in flow direction couldinduce undesired vortex mixing of the buffy coat materials into theplasma. The presence of the radial ledge 238 in the opening 236 alsopromotes separation of the high density fluid from the plasma,maintaining a desirably high red blood cell hematocrit.

[0171] It should be appreciated that the barrier 232 could be configuredoppositely relative to the direction of blood flow, so that the taperededge 234 directs blood along the high-G wall 208 in an axial flowdirection upward from a bottom annular boundary wall toward an upperboundary annular wall. In this arrangement, the high-G opening 236 wouldbe located adjacent and axially spaced from the upper annular boundarywall, and the removal of blood could occur from the opposite side of theprocessing chamber, i.e., the bottom annular wall side. In a radialseparation field established between high-G and low-G surfaces, theaxial flow direction (either “up” or “down” along the axis of rotation)blood takes along a high-G surface toward an annular boundary is notimportant to achieving the separation objective; rather, it is themitigation against abrupt changes in the flow direction while higher andlower density materials separated within the radial field are directedtoward their respective collection passages.

[0172] The contours, ports, channels, and walls that affect the bloodseparation process may be preformed in the base component 200 in asingle, injection molded operation, during which molding mandrels areinserted and removed through the open end of the base component 200. Thelid component 202 comprises a simple flat part that can be easily weldedto the open end of the base component 200 to close it after molding.Because all features that affect the separation process are incorporatedinto one injection molded component, any tolerance differences betweenthe base 200 and the lid 202 will not affect the separation efficienciesof the chamber 18.

[0173] If the contours, ports, channels, and walls that are preformed inthe base 200 create surfaces that do not readily permit the insertionand removal of molding mandrels through a single end of the base 200,the base 200 can be formed by separate molded parts, either by nestingcup shaped subassemblies or two symmetric halves.

[0174] Alternatively, molding mandrels can be inserted and removed fromboth ends of the base 200. In this arrangement (see FIG. 19), thechamber 18 can be molded in three pieces; namely, the base 200, the lid202 (which closes one end of the base 200 through which top moldingmandrels are inserted and removed), and a separately molded insert 242(which closes the other end of the base 200 through which bottom moldingmandrels are inserted and removed, as shown in FIG. 19.

[0175] The chamber 18 can be counterbalanced for rotation in variousways. Interior structures can be molded on one side of the chamber 18 tocounterbalance interior structures on the opposite side of the chamber18. Wall thickness can be varied about the chamber 18 to achievecounterbalancing. Alternatively, as shown in FIG. 18, the chamber 18 caninclude a molded pocket 248 to carry a suitable counterbalancing weight.

B. The Cassette and Flow Set

[0176]FIG. 23 shows the cassette 28 previously described coupled toexternal processing containers in a configuration that can be used for aplasma collection procedure. For a plasma collection procedure, thecontainers include a plasma collection container 160, a red blood cellcollection container or reservoir 162, a whole blood in-processcontainer 158, an anticoagulant container 150, and a processing fluid(e.g., saline) container 164.

1. Plasma Collection Cycle

[0177] During a typical collection cycle of the plasma collectionprocedure, whole blood drawn from the donor is processed to collectplasma, while returning red blood cells to the donor. The donorinterface pumps DP1/DP2 in the cassette, the anticoagulant pump ACP inthe cassette, the in-process pump IPP in the cassette, and the plasmapump PP in the cassette are pneumatically driven by the controller 16,in conjunction with associated pneumatic valves V1 to V26, to drawanticoagulated blood into the in-process container 158, while conveyingthe blood from the in-process container 158 into the processing chamber18 at a controlled rate QWB for separation. This arrangement alsoremoves plasma from the processing chamber 18 into the plasma container160 at a controlled rate QP, while removing red blood cells from theprocessing chamber 18 into the red blood cell container 162 (at a rateQRBC=QWB−QP). This phase continues until a targeted volume of plasma iscollected in the plasma collection container 160 (as monitored by aweigh sensor) or until a targeted volume of red blood cells is collectedin the red blood cell collection container 162 (as also monitored by aweigh sensor).

[0178] If the volume of whole blood in the in-process container 158reaches a predetermined maximum threshold before the targeted volume ofeither plasma or red blood cells is collected, the controller 16terminates operation of the donor interface pumps DP1/DP2 to terminatecollection of whole blood in the in-process container 158, while stillcontinuing blood separation. If the volume of whole blood reaches apredetermined minimum threshold in the in-process container 158 duringblood separation, but before the targeted volume of either plasma or redblood cells is collected, the controller 16 returns to drawing wholeblood to thereby allow whole blood to enter the in-process container158. The controller toggles between these two conditions according tothe high and low volume thresholds for the in-process container 158,until the targeted volume of plasma has been collected, or until thetarget volume of red blood cells has been collected, whichever occursfirst.

2. Red Blood Cell Return Cycle

[0179] During a typical return cycle (when the targeted volume of plasmahas not been collected), the controller 16 operates the donor interfacepumps DP1/DP2 within the cassette 28, the in-process pump IPP within thecassette, and the plasma pump PP within the cassette, in conjunctionwith associated pneumatic valves, to convey anticoagulated whole bloodfrom the in-process container 158 into the processing chamber 18 forseparation, while removing plasma into the plasma container 160 and redblood cells into the red blood cell container 162. This arrangement alsoconveys red blood cells from the red blood cell container 162 to thedonor, while also mixing saline from the container 164 in line with thereturned red blood cells. The in line mixing of saline with red bloodcells raises the saline temperature and improves donor comfort. Thisphase continues until the red blood cell container 162 is empty, asmonitored by the weigh sensor.

[0180] If the volume of whole blood in the in-process container 158reaches a specified low threshold before the red blood cell container162 empties, the controller 16 terminates operation of the in-processpump IPP to terminate blood separation. The phase continues until thered blood cell container 162 empties.

[0181] Upon emptying the red blood cell container 162, the controller 16operates the donor interface pump station DP1 to draw whole blood fromthe in process container 158 to fill the donor tube 126, thereby purgered blood cells (mixed with saline) in preparation for another drawwhole blood cycle. The controller 16 then conducts another collectioncycle. The controller 16 operates in successive collection and returncycles until the weigh sensor indicates that a desired volume of plasmahas been collected in the plasma collection container 160. Thecontroller 16 terminates the supply and removal of blood to and from theprocessing chamber, while operating the donor interface pumps DP1/DP2 inthe cassette 28 to convey red blood cells remaining in the red bloodcell container 162 to the donor. The controller 16 next enters an airpurge cycle, the details of which will be described later.

D. Control of the Interface

[0182] During a given plasma collection cycle, the controller 16desirably operates the sensing station 46, to monitor the presence oftargeted cellular blood species components (in particular, platelets orleukocytes, or both) in the plasma collection tube 106. The presence ofthese cellular components in the plasma, which are detected by the firstsensor 146, indicates an over spill condition—i.e., indicating that theinterface is close enough to the low-G wall of the processing chamber toallow all or some of these blood species components to be swept into theplasma collection tube 106 (see FIG. 13). This is not desirable, as theobjective is to collect plasma free or substantially free of cellularblood components (i.e., a platelet-poor plasma product)

[0183] In response to an over spill condition (shown in FIG. 13), thecontroller 16 operates the in-process pump IPP to draw whole blood fromthe in-process container 158 into the processing chamber 18 at apredetermined flow rate. Red blood cells continue to exit the chamber 18through the tube 104 for collection in the collection container 162.However, the controller 16 ceases operation of the plasma pump PP for apreestablished time period (e.g., 20 seconds). This action increases thevolume of plasma in the chamber 18 relative to the volume of red bloodcells, forcing the interface away from the low-G wall and back towardthe middle of the separation chamber (as FIG. 12 shows). After thepreestablished time period, the controller 16 resumes operation of theplasma pump PP for a short time period (e.g., 1 seconds), whilediverting the plasma to the red blood cell collection container 162 forreturn to the donor. After this time period, if the spill has beencorrected, clean plasma will be detected by the first sensor 146, andnormal plasma collection can be resumed. If clean plasma is not sensed,indicating that the over spill has not been corrected, the controller 16repeats the above-described sequence.

[0184] The above-described sequence does not rely upon ascertaining theactual physical position of the interface within the separation chamber,but instead relies upon the measurement resolution for the sensor 146 todiscern the presence of cellular components should they move too closeto the high-G wall and exit the chamber. When the prescribed maximumallowable platelet contamination is set to a desired low threshold, theplatelet contamination threshold can lay below the measurementresolution of the sensor 146. Therefore, a control scheme that reliesexclusively upon sensing an over spill condition may not be optimal.

[0185] The difference between the flow rate of whole blood entering theseparation chamber (QWB) and the flow rate of plasma exiting theseparation chamber 18 (QP) determines the flow rate of red blood cellsexiting the chamber (QRBC) (i.e., (QRBC=(QWB)−(QP)). (QWB) is typicallymaintained at a fixed desired rate to optimize processing time, whichfor a plasma collection procedure generally about 70 ml/min. The ratio(QP)/(QWB) therefore correlates to the physical position of theinterface within the separation chamber 18. At a given fixed (QWB),increases in (QP), thereby increasing the ratio, removes a greatervolume of plasma and therefore moves the interface toward the low-G wall(as FIG. 13 shows) Conversely, at a given fixed (QWB), decreases in(QP), thereby decreasing the ratio, removes a lesser volume of plasmaand therefore moves the interface toward the high-G wall (as FIG. 14shows).

[0186] The “ideal” ratio (QP)/(QWB)is one that keeps the interface in adesired position within the chamber (as FIG. 12 shows) to avoid an overspill condition in the first instance. However, the “ideal” ratio(QP)/(QWB) is a function of the hematocrit of the donor's whole blood,which cannot be readily controlled or measured during the course of ablood processing procedure.

[0187] It has been discovered that the magnitude of the hematocrit ofred blood cell exiting the chamber 18 (HCTRBC) can be used to controlthe physical position of the interface within the separation chamber 18,and thereby minimize or avoid over spill conditions. More particularly,the hematocrit of red blood cells exiting the chamber 18 (HCTRBC)increases with increasing distance between the interface and the high-Gwall (i.e., with increases in the ratio (QP)/(QWB)). Conversely, thehematocrit of red blood cell exiting the chamber 18 (HCTRBC) decreaseswith decreasing distance between the interface and the high-G wall(i.e., with decreases in the ratio (QP)/(QWB)). By adjusting the ratio(QP)/(QWB) to achieve a targeted hematocrit of red blood cells exitingthe chamber 18 (HCTRBC), a targeted physical position of the interfacerelative to the high-G wall can be achieved, without inducing an underspill or over spill condition.

[0188] As before described, the sensor 148 for the red blood cellcollection tube 104 is desirably adapted and configured to opticallydetect hematocrit HCTRBC and changes in the hematocrit of red bloodcells exiting the processing chamber 18 over time. Alternatively,various conventional means for sensing red blood cell hematocrit canalso be used.

[0189] An optimal set point for HCTRBC (SET_HCTRBC) can be selectedbased upon analysis of empirical clinical data generated during systemoperation, which correlates measured optimal plasma product quality (interms of platelet, red blood cell, and leukocyte contamination, and, inparticular, the absence thereof) and measured optimal collection time.The data demonstrates that, at a determinable high threshold HCTRBC,platelets will cease exiting the chamber 58 with red blood cells. Atthis given high threshold value HCTRBC, platelets tend to remain withthe plasma in the chamber 18, and thereby be subject to mixing with theplasma. Based upon this discovery, SET_HCTRBC is set to approach, butnot exceed, this high threshold red blood cell hematocrit value. In arepresentative implementation, SET_HCTRBC equals about 80±5. Adjustingthe ratio (QP)/(QWB) to achieve (SET_HCTRBC) during a given plasmacollection procedure serves to optimize plasma collection parameters forthat procedure, as well as mediate against or avoid over spillconditions. Using SET_HCTRBC as a control allows (QP) to be maximized tooptimize procedure time and maximize red blood cell hematocrit, whileinducing platelets to leave the chamber with the red blood cells toavoid an over spill condition.

[0190] In this arrangement, the controller 16 periodically comparessensed HCTRBC (sensed by the sensor 148) to SET_HCTRBC, and adjusts theratio (QP)/(QWB) to minimize the difference between sensed HCTRBC andSET_HCTRBC. Control based upon SET_HCTRBC keeps the interface in alocation within the separation chamber that is empirically determined tooptimize plasma purity and collection time, while avoiding or minimizingover spill conditions.

[0191] In a representative implementation, the ratio (QP)/(QWB) isdesirably set at the outset of a given plasma collection procedure to avalue that is somewhat less than an “ideal” (QP)/(QWB). In arepresentative implementation, the “ideal” (QP)/(QWB) is multiplied by adecrement factor of about 95% to set the initial ratio (QP)/(QWB). Inthis implementation, the “ideal” (QP)/(QWB) is set equal to (1−Hi/Ho),where Hi is the hematocrit of anticoagulated whole blood entering theseparation chamber 18, and Ho is SET_HCTRBC. Hi is derived based uponthe actual or estimated hematocrit of the donor (Donor_HCT) and thedilution of the whole blood as a result of addition of anticoagulant. Hican be derived, e.g., by multiplying Donor_HCT by (1 minus theanticoagulant-to-whole blood ratio/100).

[0192] As the procedure progresses, sensed HCTRBC is periodicallycompared to SET_HCTRBC, and the initial ratio (QP)/(QWB) is incrementedor decremented to minimize the difference. Preferably, to avoid an overspill condition, the increments to the ratio (QP)/(QWB) are determinedtaking into account the difference between sensed HCTRBC and SET_HCTRBCas well as the rate at which the difference is changing. ConventionalPID control techniques can be used. Desirably, the ratio (QP)/(QWB) isincremented or decremented within a set minimum and maximum range ofvalues based upon the “ideal” ratio (QP)/(QWB).

[0193] Should an over spill be encountered, it is corrected in themanner discussed above and processing then proceeds.

[0194] As above described, “ideal” (QP)/(QWB) is a function, at least inpart, of the anticoagulated whole blood hematocrit of the donor(Hi) .The donor's whole blood hematocrit can be physically measured at theoutset of a processing procedure, or be based upon an empiricallydetermined default value (e.g., 0.41 for a female donor and 0.43 for amale donor).

[0195] Since the system 10 includes a blood processing chamber 18 ofknown maximum capacity, the controller 16 can empirically derive theanticoagulated whole blood hematocrit of the donor on line at the outsetof a given blood processing procedure.

[0196] After venipuncture has been performed and the blood inlet andreturn pathways primed with whole blood, the controller 16 conditionsthe centrifuge station 20 to undergo a ramp-up phase. During the ramp-upphase, the processing chamber 18 is accelerated to blood collectionvelocity. Whole blood is pumped into the separation chamber 18. The redblood cell exit tube is closed, while the plasma exit tube is opened.The controller 16 retains this state until the sensor on the plasma tubedetects the presence of red blood cells. This occurrence indicates thatthe processing chamber 18 has been filled with anticoagulated wholeblood. With this occurrence, the controller 16 registers the volume ofwhole blood that has been conveyed into processing chamber 18. Thevolume of whole blood required to fill the processing chamber 18 willvary inversely with the donor's anticoagulated whole blood hematocrit.Since the volume of the molded processing chamber 18 is fixed and known,the anticoagulated whole blood hematocrit value for the donor can bedirectly derived from the measured volume of anticoagulated whole bloodrequired to fill it at the outset of a given processing procedure.

V. Use of the System to Perform a Double Red Blood Cell CollectionProcedure

[0197] Use of the set 12 in association with the device 14 andcontroller 16 to conduct a typical double unit red blood cell collectionprocedure will now be described for illustrative purposes.

A. The Blood Processing Chamber

[0198]FIG. 8 shows an embodiment of the centrifugal processing chamber18, which can be used in association with the system 10 shown in FIG. 1to perform the intended red blood cell collection procedure. The chamber18 shares many technical features of the chamber shown in FIG. 18 andpreviously described, and common reference numerals will be used forthis reason. As previously described, the processing chamber 18 isfabricated in two separately molded pieces; namely, the base 200 and thelid 202. The hub 204 is surrounded radially by inside and outsideannular walls 206 and 208 that define a circumferential blood separationchannel 210. A molded annular wall 214 (see FIG. 7) closes the bottom ofthe channel 210. The lid 202 closes the top of the channel 210. Whenassembled, the lid 202 is secured to the top of the chamber 18, e.g., byuse of a cylindrical sonic welding horn.

[0199] As previously described, the inside annular wall 206 is openbetween one pair of stiffening walls. The opposing stiffening walls forman open interior region 222 in the hub 204, which communicates with thechannel 210. Blood and fluids are introduced from the umbilicus 100 intoand out of the separation channel 210 through this region 222. A moldedinterior wall 224 formed inside the region 222 extends entirely acrossthe channel 210, joining the outside annular wall 208. The wall 224forms a terminus in the separation channel 210, which interrupts flowcircumferentially along the channel 210 during separation.

[0200] Additional molded interior walls divide the region 222 into threepassages 226, 228, and 230. The passages 226, 228, and 230 extend fromthe hub 204 and communicate with the channel 210 on opposite sides ofthe terminus wall 224. Blood and other fluids are directed from the hub204 into and out of the channel 210 through these passages 226, 228, and230.

[0201] As previously described, the chamber 18 can be counterbalancedfor rotation in various ways.

[0202] As the processing chamber 18 shown in FIG. 8 is rotated (arrow Rin FIG. 8) , the umbilicus 100 conveys whole blood into the channel 210through the passage 226. The whole blood flows in the channel 210 in thesame direction as rotation (which is counterclockwise in FIG. 8).Alternatively, the chamber 18 can be rotated in a direction opposite tothe circumferential flow of whole blood, i.e., clockwise, although awhole blood flow in the same direction as rotation is believed to bedesirable for blood separation efficiencies.

[0203] The whole blood separates as a result of centrifugal forces inthe manner shown in FIG. 12. Red blood cells are driven toward thehigh-G wall 208, while lighter plasma constituent is displaced towardthe low-G wall 206.

[0204] As FIG. 8 shows, a dam 244 projects into the channel 210 towardthe high-G wall 208. The dam 244 prevents passage of plasma, whileallowing passage of red blood cells into a channel 246 recessed in thehigh-G wall 208.

[0205] The channel 246 directs the red blood cells into the umbilicus100 through the radial passage 230. The plasma constituent is conveyedfrom the channel 210 through the radial passage 228 into umbilicus 100.

[0206] Because the red blood cell exit channel 246 extends outside thehigh-g wall 208, being spaced further from the rotational axis than thehigh-g wall, the red blood cell exit channel 246 allows the positioningof the interface between the red blood cells and the buffy coat veryclose to the high-g wall 208 during blood processing, without spillingthe buffy coat into the red blood cell collection passage 230 (creatingan over spill condition). The recessed exit channel 246 thereby permitsred blood cell yields to be maximized (in a red blood cell collectionprocedure) or an essentially platelet-free plasma to be collected (in aplasma collection procedure).

[0207] As before described, the contours, ports, channels, and wallsthat affect the blood separation process may be preformed in the base200 in a single, injection molded operation, during which moldingmandrels are inserted and removed through the open end of the base 200.If the contours, ports, channels, and walls that are preformed in thebase 200 create surfaces that do not readily permit the insertion andremoval of molding mandrels through a single end of the base 200, thebase 200 can be formed by separate molded parts, either by nesting cupshaped subassemblies or two symmetric halves, or by removal of moldingmaterials through both ends of the base 200 and use of inserts 242, asFIG. 19 shows.

B. The Cassette

[0208] The interior configuration of pump chambers, valves, and fluidpaths for cassette 28 used for the double unit red blood cell procedureis the same as the cassette 28 used for the plasma procedure, and commonreference numbers are used for this reason. FIG. 24 shows the cassette28 previously described coupled to external processing containers in aconfiguration that can be used for a double unit red blood cellcollection procedure. For a double unit red blood cell collectionprocedure, the containers include the same array of containers used forthe plasma collection procedure; namely, a plasma collection container160, a red blood cell collection container or reservoir 162, a wholeblood in-process container 158, an anticoagulant container 150, and aprocessing fluid (e.g., saline) container 164. For a double unit redblood cell collection procedure, additional containers are used; namely,a red blood cell additive solution container 168 and a leukocytereduction collection assembly 176 comprising a leukocyte removal filter170 and one or more red blood cell storage containers 172 and associatedtubing 178. FIGS. 5 and 6 show the mounting of cassette 28 andcollection containers shown in FIG. 24 on the device for a double unitred blood cell collection procedure.

1. Collection Cycle

[0209] During a typical collection cycle of the double unit red bloodcell collection procedure, whole blood drawn from the donor is processedto collect two units of red blood cells, while returning plasma to thedonor. The donor interface pumps DP1/DP2 in the cassette, theanticoagulant pump ACP in the cassette, the in-process pump IPP in thecassette, and the plasma pump PP in the cassette are pneumaticallydriven by the controller 16, in conjunction with associated pneumaticvalves, to draw anticoagulated blood into the in-process container 158,while conveying the blood from the in-process container 158 into theprocessing chamber 18 for separation. This arrangement also removesplasma from the processing chamber into the plasma container 160, whileremoving red blood cells from the processing chamber into the red bloodcell container 162. This phase continues until an incremental volume ofplasma is collected in the plasma collection container 160 (as monitoredby a weigh sensor) or until a targeted volume of red blood cells iscollected in the red blood cell collection container 162 (as monitoredby a weigh sensor).

[0210] If the volume of whole blood in the in-process container 158reaches a predetermined maximum threshold before the targeted volume ofeither plasma or red blood cells is collected, the controller 16terminates operation of the donor interface pumps DP1/DP2 to terminatecollection of whole blood in the in-process container 158, while stillcontinuing blood separation. If the volume of whole blood reaches apredetermined minimum threshold in the in-process container 158 duringblood separation, but before the targeted volume of either plasma or redblood cells is collected, the controller 16 returns to drawing wholeblood to thereby allow whole blood to enter the in-process container158. The controller toggles between these two conditions according tothe high and low volume thresholds for the in-process container 158,until the requisite volume of plasma has been collected, or until thetarget volume of red blood cells has been collected, whichever occursfirst.

2. Return Cycle

[0211] During a typical return cycle (when the targeted volume of redblood cells has not been collected) , the controller 16 operates thedonor interface pumps DP1/DP2 within the cassette 28, the in-processpump IPP within the cassette, and the plasma pump PP within thecassette, in conjunction with associated pneumatic valves, to conveyanticoagulated whole blood from the in-process container 158 into theprocessing chamber 18 for separation, while removing plasma into theplasma container 160 and red blood cells into the red blood cellcontainer 162. This arrangement also conveys plasma from the plasmacontainer 160 to the donor, while also mixing saline from the container164 in line with the returned plasma. The in line mixing of saline withplasma raises the saline temperature and improves donor comfort. Thisphase continues until the plasma container 160 is empty, as monitored bythe weigh sensor.

[0212] If the volume of whole blood in the in-process container 158reaches a specified low threshold before the plasma container 160empties, the controller 16 terminates operation of the in-process pumpIPP to terminate blood separation. The phase continues until the plasmacontainer 160 empties.

[0213] Upon emptying the plasma container 160, the controller 16conducts another collection cycle. The controller 16 operates insuccessive collection and return cycles until the weigh sensor indicatesthat a desired volume of red blood cells have been collected in the redblood cell collection container 162. The controller 16 terminates thesupply and removal of blood to and from the processing chamber, whileoperating the donor interface pumps DP1/DP2 in the cassette 28 to conveyplasma remaining in the plasma container 160 to the donor. Thecontroller 16 next operates the donor interface pumps DP1/DP2 in thecassette to convey the blood contents remaining in the in-processcontainer 158 to the donor as well as convey saline to the donor, untila prescribed replacement volume amount is infused, as monitored by aweigh sensor.

3. Forced Under Spill (Final Red Blood Cell Purge)

[0214] In an alternative embodiment, the controller 16 shortens theoverall procedure time by causing a forced under spill of red bloodcells from the separation chamber into the red blood cell collectioncontainer near the end of the procedure. The deliberately forced underspill purges residual red blood cell volume from the separation chamberat the end of a procedure, thereby simplifying and shortening the timeof collection and the final return cycle.

[0215] In this embodiment, the controller 16 periodically or constantlymonitors the volume of red blood cells remaining to be collected duringa given procedure. The controller 16 commences the forced under spillcondition when the volume of red blood cells remaining to be collectedequals or approximates the volume of red blood cells occupying theseparation chamber 18. The volume of red blood cells occupying theseparation chamber can be derived based upon (i) the area of theseparation chamber 18 (KA) (which is a known quantity based upongeometry of the chamber); (ii) the change in interface position during ared blood cell purge (KI)(which is also a known quantity based ongeometry of the chamber); (iii) inlet anticoagulated whole bloodhematocrit (Hi), the derivation of which has been previously described,or which can comprise a default value dependent upon gender; (iv) outletred blood cell hematocrit HCTRBC, the derivation of which has also beenpreviously described; and (v) the absolute volume of red blood cellspresent in the chamber 18 at the start of the red blood cell purgesequence (KRBC) (which is a constant based upon the geometry of theseparation chamber 18). Representative algorithms for deriving thevolume of red blood cells occupying the separation chamber based uponthe above factors (Forced Under SpillRBC) are:

Forced Under SpillRBC=(KRBC)+ΔIP*HCTRBC

[0216] where: ΔIP is the in process blood volume needed to achieve theunder spill=(KI)/[(1−(Hi))/HCTRBC/(KA)]

[0217] During the forced under spill, the red blood cell collection tube104 is closed and the plasma collection tube 106 is opened. In thisstate, the platelet and leukocyte layer of the interface is conveyedfrom the chamber 18 along with the plasma for return to the donor.

[0218] This reduces leukocyte contamination of the red blood cells. Whenthe controller 16 detects that red blood cells have entered the plasmacollection tube 106 (which the sensor 146 will detect), the controllercloses the plasma collection tube and opens the red blood cellcollection tube. This state allows the red blood cells that haveaccumulated in the separation chamber to be conveyed to the red bloodcell collection container. Typically, the blood cell collection targetis achieved during this state. If that target is not reached, thecontroller 16 reverts to a normal red blood cell collection state.

[0219] Upon completion of a red blood cell collection procedure, thecontroller 16 enters an air purge cycle, the details of which will bedescribed later. 4. Leukofiltration

[0220] When the collection of red blood cells and the return of plasmaand residual blood components have been completed, the controller 16 canswitch, either automatically or after prompting the operator, to anin-line leukofiltration cycle. During this cycle, red blood cells areremoved from the red blood cell collection reservoir 162 and conveyedinto the red blood cell storage containers 172 through the leukocyteremoval filter 170. At the same time, a desired volume of red blood cellstorage solution from the container 168 is mixed with the red bloodcells.

[0221] The leukofilter 170 can be variously constructed. The filter can,e.g., comprise a housing inclosing a filtration medium that can comprisea membrane or be made from a fibrous material, such as melt blown orspun bonded synthetic fibers (e.g., nylon or polyester orpolypropylene), semi-synthetic fibers, regenerated fibers, or inorganicfibers. If fibrous, the medium removes leukocytes by depth filtration.If a membrane, the medium removes leukocytes by exclusion. The housingcan comprise rigid plastic plates sealed about their peripheries.Alternatively, the housing can comprise flexible sheets of medical gradeplastic material, such as polyvinyl chloride plasticized withdi-2-ethylhexyl-phthalate (PVC-DEHP). The filter 170 can be held duringuse in a retaining fixture 182 on the base of the device.

[0222] In the first stage of the leukofiltration cycle, the controller16 operates donor interface pumps DP1/DP2 in the cassette to draw airfrom the red blood cell storage containers 172, the filter 170, and thetubing 178, and to transfer this air into the red blood cell collectionreservoir 162. This stage minimizes the volume of air residing in thered blood cell storage containers 172 before the leukocyte removalprocess begins. The stage also provides a volume of air in the red bloodcell collection container 162 that can be used purge red blood cellsfrom the filter 170 into the red blood cell collection containers 172once the leukocyte removal process is completed.

[0223] In the next stage, the controller 16 operates the donor interfacepumps DP1/DP2 in the cassette 28 to draw a priming volume of storagesolution from the solution container 168 into the red blood cellcollection reservoir 162. This stage primes the tubing 180 between thecontainer 168 and the cassette 28, to minimize the volume of air pumpedinto the final red blood cell storage containers 172.

[0224] In the next stage, the controller 16 operates the donor interfacepumps DP1/DP2 in the cassette 28 to alternate pumping red blood cellsfrom the red blood cell collection reservoir 162 into the red blood cellcollection containers 172 (through the filter 170), with pumping of redblood cell storage solution from the container 168 into the red bloodcell collection containers 172 (also through the filter 170). Thisalternating process mixes the storage solution with the red blood cells.The controller 16 counts the pneumatic pump strokes for red blood cellsand the storage solution to obtain a desired ratio of red cell volume tostorage solution volume (e.g., five pump strokes for red blood cells,followed by two pump strokes for storage solution, and repeating thealternating sequence). This alternating supply of red blood cells andstorage solution continues until the weigh scale for the red blood cellcollection reservoir 162 indicates that the reservoir 162 is empty.

[0225] When the red blood cell collection reservoir 162 is empty, thecontroller 16 operates the donor interface pumps DP1/DP2 to pump apredetermined volume of air from the red blood cell collection reservoir162 through the filter 170. The volume of air is predetermined basedupon the volume of air that was drawn into the red blood cell collectionreservoir 308 before the leukocyte removal process began. The air servesto purge red blood cells from the filter 170, to minimize the presenceof residual red blood cells in the tubing, cassette 28, and filter 170.This step also assures that the red blood cell collection reservoir 162is completely empty.

[0226] The controller 16 next pumps additional storage solution throughthe filter 170 and into the red blood storage containers 172, asrequired to ensure that a desired ratio between storage solution volumeand red blood cell volume exists. Then, as a final step, the controller16 pumps a last, predetermined volume of storage solution through thefilter 170 to rinse any still-remnant red blood cells from the filter170 and into the storage containers 172. This final step maximizespost-filtration percent red blood cell recovery. The controller 16desirably waits a predetermined time period (e.g., 20 seconds) to allowthe filter 170 to complete draining.

[0227] Further details of the leukofiltration cycle and theleukofiltration filter 170 can be found in Co-Pending U.S. patentapplication Ser. No. 09/976,832, filed Oct. 13, 2001, and entitled“Blood Separation Systems and Methods that Alternate Flow of BloodComponent and Additive Solution through an In-Line Leukofilter,” whichis incorporated herein by reference.

VI. Air Purge

[0228] At the end of a given blood collection procedure, the chamber 18will contain residual volumes of red blood cells and plasma. It isdesirable to return these residual volumes of blood components to thedonor. This is particularly true in the case of red blood cells. Theability to return as many red blood cells as possible minimizes donorred blood cell loss and shortens the subsequent deferral period, duringwhich collection of red blood cell from the donor is not permitted.

[0229] It has been discovered that the most efficient way to flush redblood cells from the separation chamber for return to the donor is bysending sterile air through the separation chamber. The use of sterileair, instead of a liquid, to flush red blood cells from the separationchamber after blood processing also lessens the weight of potentiallybio-hazardous wastes that must be disposed of after blood processing.

[0230] Sterile air is purged from the system and parked in thein-process whole blood reservoir during the initial priming cycle, priorto a given blood processing procedure. This becomes the source ofsterile air to subsequently flush red blood cells from the separationchamber after completion of the blood processing procedure.

[0231] During a first phase of the air flush, the red blood cellcollection tube 104 is closed. Air is pumped through the whole bloodinlet tube 102 into the separation chamber 18, while residual red bloodcells are drawn by operation of the plasma pump PP through the plasmaoutlet tube 106 from the chamber 18. This phase continues until air isdetected in the plasma tube 106. A second phase of the air flush thencommences.

[0232] During the second phase, the plasma outlet tube 106 is closed,and the red blood cell tube 104 is opened. The separation chamber 18 isramped into rotation to achieve a relatively modest rotational rate(e.g., 300 RPM), sufficient to displace red blood cells toward thehigh-G wall of the chamber 18 for removal, and to displace air residingin the separation chamber 18 toward the low-G wall of the separationchamber 18. The second phase continues until air is detected in the redblood cell tube 104. At this point, the air flush is terminated.

[0233] The detection of air in the red blood cell tube 104 and theplasma tube 106 can be accomplished using a conventional ultrasonic airdetector. However, it has been discovered that the same sensors 146 and148 used for optically detecting cellular components in the plasma andred blood cell tubes 106 and 104 can also be used to detect the presenceof air in these tubes 106 and 104.

[0234] As previously described, the sensor 146 in the plasma tube 106uses red and green light transmission to determine the concentrations ofplatelets and/or red blood cells in plasma exiting the chamber 18. Thesensor 148 in the red blood cell tube 104 uses infrared (805 nm)reflectance and transmission to determine the hematocrit of red bloodcells exiting the separation chamber 18. The sensors 146 and 148 areoperated by the controller 16, which periodically actuates the sensors146 and 148 and samples the outputs. A given sensor output is theaverage of multiple samples.

[0235] It is been determined that the present of air bubbles passing byeither sensor 146 or 148 creates a pronounced variance among themeasurement samples taken by the sensor, which significantly exceeds thevariance used to validate sample averages during normal operation. A setthreshold variance among samples taken during a sample period can becorrelated to the presence of air during the air flush cycle. Thevariance of multiple samples taken during a given sampling period can bedetermined, e.g., by summing the difference between each sample and thesample average, squaring the sum of the differences, and dividing thisquantity by the number of samples minus one.

[0236] In the case of the plasma line sensor 146, if the variance foreither red or green transmittance measurements exceeds a thresholdvariance of about 4000 (which is greater than the variance by which thevalidity of samples are gauged for normal interface sensing purposes),the controller 16 generates an air bubble detection signal for theplasma tube 106. The controller 16 shifts from first phase to the secondphase of the air flush protocol.

[0237] In the case of the red blood cell line sensor 148, if thevariance of either infrared transmittance or infrared reflectancemeasurements exceeds a threshold variance of about 2000 (which is alsogreater than the variance by which the validity of samples are gaugedfor normal interface sensing purposes), the controller 16 generates anair bubble detection signal for the red blood cell tube 104. Thecontroller 16 terminates the second phase of the air flush protocol.

VII. Cassette Integrity Checks

[0238] Installation of the blood flow set 12 involves correct placementof the cassette 28 in the pump and valve station 30, correct routing ofthe donor tube 126 and anticoagulant tube 152 through the donor clamp154, and the correct placement of a clamp 116 or a hemostat downstreamof the donor tube-anticoagulant tube 152 junction. The correct placementof the cassette, correct routing of these tubes 126 and 152 through thedonor clamp 154, and the presence of a clamp 116 or a hemostat isdesirably checked in every procedure prior to connecting the donor tothe flow set.

[0239] A pneumatic seal between cassette diaphragm 304 and the pneumaticmanifold assembly 34 is necessary to ensure proper functioning of fluidpressure-actuated valves and pumps, as well as the integrity of thefluid flow channels within the cassette. In addition to a pneumaticseal, the amount of trapped air between cassette diaphragm 304 and valveface gasket 318 of the pneumatic manifold assembly 34 should beminimized for effective operation of fluid valves and pumps. Inflationof the door bladder 314 prior to complete installation of cassette 28against the manifold assembly 34 can compromise sealing. Defects incassette sealing surfaces, like knicks and dings, as well as improperloading of cassette 28 in the cassette holder 26 can also compromisesealing. These conditions also are desirably detected prior toconnecting the donor to the flow set 12.

[0240] For these reasons, the controller 16 desirably undertakes aseries of cassette installation and integrity checks. In arepresentative implementation, these installation and integrity checksinclude (1) a cassette presence check, which verifies the presence ofcassette 28 in the pump and valve station 30 prior to inflation of doorbladder 314; (2) a burp routine to minimize trapped air between cassettediaphragm 304 and valve face gasket 318; (3) a valve cross-talk check,which verifies proper seating of cassette 28 against the manifoldassembly 34 and the lack of leaks in the valve face gasket 318; (4) adry cassette integrity test, which verifies—using air—the correctrouting of the donor tube 126 and the anticoagulant tube 152 throughdonor clamp 154; and (5) a wet cassette integrity test, whichverifies—using a liquid (e.g., saline)—the absence of cassette defectswhich could compromise sealing of valves and integrity of fluidchannels.

A. Cassette Presence Check

[0241] This test verifies that a cassette 28 is installed and the door32 of the pump and valve station 30 is closed prior to connecting adonor and starting a desired blood processing session.

[0242] With reference to FIG. 15, the operator installs the cassette 28in the pump and valve station 30 and closes the station door 32. If thecassette 28 is present, the available volume for expansion of doorbladder 314 is reduced. Therefore, the time required to reach a givenpressure level is reduced. This property is used during the cassettepresence check to verify the presence of cassette 28 in the pump andvalve station 30.

[0243] The controller 16 directs the manifold assembly 34 to applyvacuum to open all cassette valves and pumps. The controller 16 thendirects the manifold assembly 34 to apply pneumatic pressure to the doorbladder 314. The controller 16 registers the build-up of pressure in thebladder 314, while also tracking elapsed time. If the pressure in thebladder 314 equals or exceeds a prescribed threshold pressure (PBLAD)(e.g., 800 mmHg) within a prescribed time period (e.g., 30 seconds), thecontroller 18 deems that the cassette 28 is present within the station.Otherwise, the controller 16 alarms and prompts the operator to load thecassette 28.

[0244] Once the presence of the cassette 28 is verified, the controller18 proceeds to the next integrity test, which is the burp routine.

B. Burb Routine

[0245] The burb routine minimizes the amount of air trapped betweenvalve face gasket 318 and cassette diaphragm 304, after the door 32 hasbeen closed (in general, see FIG. 15). Trapped air can adversely affectthe performance of valves and pumps in the cassette 28.

[0246] The controller 16 invokes the burb routine after the presence ofthe cassette 28 has been verified. During the burb routine, the doorbladder 314 is inflated to a prescribed lesser pressure level (e.g.,less than about 800 mmHg), which seats the cassette 28 against themanifold assembly 34, but does not cause a pneumatic seal with the valveface gasket 318. While the door bladder 314 is at this lesser pressure,the controller 16 then directs the manifold assembly 34 to regulatePHARD and then PGEN for prescribed time periods. This regulation ofdifferent pressures against the valve face gasket 318 causes the valveface gasket 318 to puff. This action will expel residual air trappedbetween the cassette diaphragm 304 and the valve face gasket 318. Thisaction is conducted for a predetermined time period, after which thedoor bladder pressure is regulated to its full, designated sealingpressure (e.g., about 900 mmHg). The controller 18 proceeds to the nextintegrity test, which is the valve cross-talk test.

C. Valve Cross-Talk Test

[0247] The objective of the valve cross-talk test is to detect leaks inthe valve face gasket 318 prior to start of a saline prime of the flowset 12. The controller 16 directs the manifold assembly 34 to set thedoor bladder 314 to sealing pressure. Adjacent valves and pump chambersare grouped by the controller 16 into pressure and vacuum categories,e.g., as follows (refer to FIG. 25A for a schematic overview view of thearrangement of these valves): Pressure V1; V3; V5; V7; V10; V12; V14;V16; V17; V18; V21; V24; V26; DP1; DP2; and ACP Vacuum V2; V4; V6; V8;V9; V11; V13; V15; V19; V20; V22; V23; V25; IPP; and PP

[0248] The controller 16 directs the manifold assembly 34 tosequentially apply PHARD, PGEN to the pressure regions and to applyVHARD and VGEN to the vacuum regions. The pressure leak rate for eachregion at each pressure/vacuum level is determined and compared to anacceptable specified level (e.g., less than about 2 to 3 mmHg/sec) . Thecontroller generates an alarm if any region experiences a leak rateequal to or greater than the specified acceptable level, which indicatesleaks in the valve face gasket 318.

[0249] If all regions experience a leak rate less than the specifiedacceptable level, the controller 18 proceeds to the next integrity test,which is the dry cassette integrity test.

D. Dry Cassette Integrity Test

[0250] The dry cassette integrity check detects misload conditionsdealing with donor tube 126 and anticoagulant tube 152 prior toperforming a saline prime of the flow set. The misload conditions can beany one or a combination of (1) the donor tube 126 and/or anticoagulanttube 152 bypassing the donor clamp 154; (2) the donor tube 126 and/orthe anticoagulant tube 152 being pinched; (3) the absence of the clamp116 or a hemostat at the donor tube 126/anticoagulant tube 152 junction.In addition to misload conditions, the test can also detect defects inthe flow set, such as pin holes or broken ports in the donor tube 126,anticoagulant tube 152, or anticoagulant container 150, which may haveoccurred after quality assurance testing following manufacture, e.g.,during shipment and handling prior to use.

[0251] The dry cassette integrity test pressurizes selected regions ofthe cassette 28 using air. The dry cassette integrity test uses airinstead of liquid, so that proper cassette installation can beascertained before fluid is introduced into the cassette 28. Thus, if amisload is detected, the cassette 28 can be readily reinstalled in anunused, sterile condition.

[0252] During a dry cassette integrity test (as schematically depictedin FIGS. 25A/25B and 26A/26B), the controller 16 directs the manifoldassembly 34 to actuate designated pump chambers in the cassette 28 todraw air from the umbilicus 100 into a selected region, and to closedesignated valves to hold pressure within the region. The initialpressure is sensed in a pump chamber communicating with the region. Thepump chamber is coupled to the targeted tube through the donor clamp154, which is set to a closed condition. The manifold assembly 34 isdirected to apply positive pressure to the pump chamber serving theregion, to try to expel air from the pump chamber. A final pressure issensed after a specified time period. If the targeted donor tube 126 oranticoagulant tube 152 is properly loaded in the donor clamp 154, thedonor clamp 154 should prevent air flow and thereby prevent a pressuredrop from occurring. If a pressure drop ratio (final pressure/initialpressure) is experienced that is greater than a predetermined threshold,the donor clamp 154 is not preventing air flow, and a misload is deemedto exist.

[0253] In a representative implementation, the dry cassette integritytest comprises two phases. In the first phase, misload conditionsdealing with the donor tube 126 are detected. In the second phase,misload conditions of the anticoagulant tube 152 are detected.

1. Phase 1 (Misload Condition of Donor Tube)

[0254] The condition of the fluid circuit 306 at the outset of Phase 1is shown in FIG. 25A.

[0255] During Phase 1, the controller 16 regulates PGEN, PHARD, VGEN,and VHARD to system pressure levels. The donor clamp 154 is opened, andthe entire cassette 28 is vented to the blood processing chamber 18. Allcassette valves are then closed, except for the valves in a path thatallows air to be drawn from the umbilicus into the donor pump chamberDP1 by operation of the plasma pump PP. In the fluid circuit 306, thispath can be created, e.g., by opening V2/V21 (opening the red blood celltube 104 from the umbilicus 100 to the red blood cell container 162);opening V1/V16 (opening the whole blood tube 102 into the umbilicus 100to the in-process container 158 through the in-process pump PPP; andopening V5/V6/V10/V11/V17 (opening the plasma tube 106 from theumbilicus 100 to the donor pump DP1 through the plasma pump PP). Thedonor clamp 154 is closed, as are the other valves in the fluid circuit306.

[0256] The controller 16 directs the manifold assembly 34 to actuate theplasma pump PP for a designated number of pump strokes. This draws airfrom the umbilicus 100 into donor pump DP1 (as shown by the arrow AIRpath in FIG. 25A).

[0257] The controller 16 then directs the manifold assembly 34 to closeV6, which closes the air path from the umbilicus 100. The controllerthen directs the manifold assembly 34 to open valves V12/V13/V18, whichopens a path from the donor pump PP1 to the donor tube 126, regulatedonly by the donor clamp 154, which remains closed. The condition of thefluid circuit 306 at this stage of Phase 1 is shown in FIG. 25B.

[0258] The controller 16 next directs the manifold assembly 34 to holdPGEN and VHARD, vent VGEN, and, after a prescribed delay period, recordthe initial PGEN1 in the donor pump DP1.

[0259] The controller 16 then directs the manifold assembly 34 to applypressure to DP1 for a prescribed period of time. This directs air fromthe donor pump DP1 toward the donor clamp 154, as shown by the arrow AIRpath in FIG. 25B. The controller 16 records existing PGEN2.

[0260] If the ratio PGEN2/PGEN1 is less than a specified value, thecontroller 16 deems that leakage of air has occurred through the donorclamp 154, and that the donor tube 126 is not properly installed in thedonor clamp 154. The controller 16 prompts the operator to reinstall thecassette 28. If the ratio PGEN2/PGEN1 is equal to or greater than thespecified value, the controller 16 deems that leakage of air through thedonor clamp 154 did not occur, and that the donor tube 126 is properlyinstalled in the donor clamp 154. In this instance, the controller 16moves to Phase 2 of the dry cassette integrity test.

2. Phase 2 (Misload Conditions of Anti-coagulant Tube)

[0261] The condition of the fluid circuit 306 at the outset of Phase 2is shown in FIG. 26A.

[0262] At the outset of Phase 2, the controller regulates PGEN, PHARD,VGEN, and VHARD to system pressure levels. The donor clamp 154 isopened, and the entire cassette 28 is vented to the blood processingchamber 18. All cassette valves are closed, except for the valves thatestablish a path that allows air to be drawn from the umbilicus 100 intothe anticoagulant pump chamber ACP through the plasma pump PP, donorpump PP1, and the donor clamp 154. In the fluid circuit 306, this pathcan be created, e.g., by opening V2/V21 (opening the red blood cell tube104 from the umbilicus 100 to red blood cell container 162); openingV1/V16 (opening the whole blood tube 102 into the umbilicus 100 fromin-process container 158 through the in-progress pump PPP; openingV5/V6/V10/V11/V17 (opening the plasma tube 106 from the umbilicus 100 todonor pump DP1 through the plasma pump PP); and opening V12/V13/V22(opening the donor tube 126 from the donor pump PP1, through donor tube126 and anticoagulant tube 152 into anticoagulant pump chamber ACP). Theclamp 116 or a hemostat is also clamped closed. The controller 16directs the manifold assembly 34 to actuate the plasma pump PP for adesignated number of pump strokes. This draws air from the umbilicus 100into anticoagulant pump ACP, through the junction of the donor tube 126and anticoagulant tube 152 (as shown by the arrow AIR path in FIG. 26A).The controller 16 then directs the manifold assembly 34 to close V22 andthe donor clamp 154, keeping the remainder of the path to the umbilicus100 open.

[0263] The controller 16 next directs the manifold assembly 34 to holdPGEN and VHARD, vent VGEN, and, after a prescribed delay period, recordthe initial PGEN1. The controller 16 then directs the manifold assembly34 to apply pressure to ACP while opening V22 for a prescribed period oftime. Air flow beyond V22 through the anticoagulant tube 152 isregulated only by the donor clamp 154, which remains closed. Thecontroller 16 records existing PGEN2. The condition of the fluid circuit306 at this stage of Phase 2 is shown in FIG. 26B, with the arrow AIRpath from ACP to the donor clamp 154 indicated.

[0264] If the ratio PGEN2/PGEN1 is less than a specified value, thecontroller deems that leakage of air occurred through the donor clamp154, and that the anticoagulant tube 152 is not properly installed inthe donor clamp 154. The controller prompts the operator to reinstallthe cassette 28. If the ratio PGEN2/PGEN1 is equal to or greater thanthe specified value, the controller deems that leakage of air throughthe donor clamp 154 did not occur, and that the anticoagulant tube 152is properly installed in the donor clamp 154. In this instance, thecontroller moves to the final integrity check, which is the wet cassetteintegrity check.

E. Wet Cassette Integrity Check

[0265] The wet cassette integrity check is designed to detect defectsrelated to product quality and donor safety that may occur in thecassette 28 itself. The check is conducted after the fluid circuit hasbeen completely primed with a priming fluid, e.g., saline. The checkuses capacitive sensing to determine the ability of the fluid circuit tomaintain a pneumatic seal in selected test regions when the fluidpathways are filled with the priming fluid.

[0266] During the wet cassette integrity tests, a selected test regionthat includes at least one pump chamber is created. The test region ispneumatically sealed from the remainder of the fluid circuit 306 byclosing valves about the boundary of the test region. During the test,the pump chamber is filled with priming fluid. The controller 16conditions the manifold assembly 34 to attempt to empty the primingfluid from the pump chamber into the enclosed test region. Usingcapacitive sensing, the controller 16 assesses the volume of fluidremaining in the chamber after the emptying attempt is made. If thevolume of fluid remaining in the pump chamber after the attempt isgreater than a predetermined minimum volume, the controller 16 deemsthat the test region was pneumatically sealed sufficiently to resistleakage of fluid from the test region. If the volume of fluid remainingin the pump chamber after the attempt is equal to or less than thepredetermined minimum volume, the controller 16 deems that leakage offluid out of the test region has occurred, and a defect alarm isgenerated. The testing desirably creates and tests a sequence of testregions in succession.

[0267] The boundary of the various test regions can be defined byevaluating the various possible sealing failure modes that the circuitcan experience.

[0268] In a representative implementation, the controller 16 opens thefollowing valves to create a first targeted test region: V3; V5; V6; V7;V15; V20; V25. FIG. 27 shows the test region in bold solid lines. Thetest region includes the donor pump DP1 and DP2, and the test regionincludes a path through which blood and blood components are conveyed toand from the donor.

[0269] The controller 16 operates the donor pump DP1/DP2 and actuatesthe appropriate valves to draw saline from the saline container 164 intothe test region, to pressurize the test region with saline to apredetermined sensed pressure. The pump chambers DP1/DP2 are filled withsaline in the process.

[0270] In FIG. 27, the test region is pneumatically sealed by boundaryvalves V2, V4, V10, V8, V13, and V14. The controller 16 desirably opensadditional valves downstream of the boundary valves to provide leakpaths that fluid exiting the test region through the boundary valves canfollow, thereby creating a more sensitive test of the specific boundaryvalves themselves. In FIG. 27, the following valves downstream of theboundary valves can be opened to provide leak paths: V1; V11; V17; V22;V23; the anticoagulant pump ACP; the plasma pump PP; the in-process pumpIPP; and the donor clamp 154. The possible fluid leak paths are shown inphantom lines in FIG. 27, with the valves outside of the boundary valvesthat can be opened in the leak paths marked with an asterisk (*)

[0271] The controller 16 isolates the pump chambers DP1/DP2 by closingvalves V6/V7/V13/V14 and, by capacitive sensing, records the pump fillvolumes for each chamber. The controller 16 opens the region under testto the donor pump by opening valves V6 and V7 and close donor pumpchambers DP1 and DP2 for a predetermined shortened push time to movefluid into the test region. The controller 16 then closes valves V6 andV7 and waits for a sample delay period. The controller 16 then obtainscapacitance sensor readings. If the final values for either pump chamberis less than a threshold minimum value (which can, e.g., represents abaseline volume above a completely empty chamber), fluid leakage fromthe test region has occurred. An alarm is generated. If the final valuesfor both pump chambers are equal to or greater than the thresholdminimum, fluid leakage has not occurred, and the test proceeds.

[0272] The integrity of another test region can be tested by opening thefollowing valves: V5; V6; V7; V15; V20; V25. FIG. 28 shows this testregion in bold solid lines. The controller 16 can open the followingvalves downstream of the boundary valves to provide fluid leak paths tocreate a more sensitive test: V11; V17; V21; V22; V23; the anticoagulantpump ACP; the plasma pump PP; the in-process pump IPP; and donor clamp154. The fluid leak paths are shown in phantom lines in FIG. 28, withthe valves outside of the boundary valves that can be opened in the leakpaths marked with an asterisk (*).

[0273] The donor pump DP1/DP2 is actuated for a predetermined number ofpump strokes to pressurize the region under test with saline from theexternal saline container 164. During this time, the donor pump chambersDP1 and DP2 are filled with saline from the saline container 164. Thecontroller 16 isolates the pump chambers DP1/DP2 by closing valvesV6/V7/V13/V14 and, by capacitive sensing, records the pump fill volumesfor each chamber. The controller 16 opens the region under test to thedonor pump DP1/DP2 by opening valves V6 and V7 and close donor pumpchambers DP1 and DP2 for a predetermined shortened push time to movefluid into the test region. The controller 16 then closes valves V6 andV7 and waits for a sample delay period. The controller 16 then obtainscapacitance sensor readings. If the final values for either pump chamberis less than a threshold (which represents a baseline volume above anempty chamber), fluid leakage into the test region has occurred. Analarm is generated. If the final values for both pump chambers are equalto or greater than a threshold (which represents a baseline volume abovean empty chamber), fluid leakage has not occurred, and the testproceeds.

[0274] The integrity of another test region can be tested by opening thefollowing valves, the following valves are opened to create yet anothertest region: V4; V13; V14; V15; and V20. FIG. 29 shows the test regionin bold solid lines. As in the preceding test regions, the followingvalves downstream of the boundary valves can opened to create leakpaths: V3; V5; V10; V11; V21; V22; V23; the anticoagulant pump ACP; theplasma pump PP; the in-process pump IPP; and the donor clamp 154. Thefluid leak paths are shown in bold phantom lines in FIG. 29, with thevalves outside of the boundary valves that can be opened in the leakpaths marked with an asterisk (*).

[0275] The donor pump DP1/DP2 is actuated for a predetermined number ofpump strokes to pressurize the region under test with saline from thein-process container 158, by passing the umbilicus 100. During thistime, the donor pump chambers DP1 and DP2 are filled with saline. Thecontroller 16 isolates the pump chambers DP1/DP2 by closing valvesV6/V7/V13/V14 and, by capacitive sensing, records the pump fill volumesfor each chamber. The controller 16 opens the region under test to thedonor pump by opening valves V13 and V14 and close donor pump chambersDP1 and DP2 for a predetermined shortened push time to move fluid intothe test region. The controller 16 then close valves V13 and V14 andwaits for a sample delay period. The controller 16 then obtainscapacitance sensor readings. If the final values for either pump chamberis less than a threshold (which represents a baseline volume above anempty chamber), fluid leakage into the test region has occurred. Analarm is generated. If the final values for both pump chambers are equalto or greater than a threshold (which represents a baseline volume abovean empty chamber), fluid leakage has not occurred, and the three-phasetest of the representative implementation is concluded.

[0276] Of course, other test regions could be established and testedaccording to the above-described rationale.

[0277] Following the battery of cassette integrity tests, venipunctureand blood processing using the system 10 can proceed.

VIII. Conclusion

[0278] The many features of the invention have been demonstrated bydescribing their use in separating whole blood into component parts forstorage and blood component therapy. This is because the invention iswell adapted for use in carrying out these blood processing procedures.It should be appreciated, however, that the features of the inventionequally lend themselves to use in other processing procedures.

[0279] For example, the systems and methods described, which make use ofa programmable cassette in association with a blood processing chamber,can be used for the purpose of washing or salvaging blood cells duringsurgery, or for the purpose of conducting therapeutic plasma exchange,or in any other procedure where blood is circulated in an extracorporealpath for treatment. Furthermore, the systems and methods described arenot limited to the processing of human or animal blood drawn fromvascular circulatory systems, but can also be used to process orseparate suspensions created outside vascular circulatory systems andcontaining cellular blood components or matter recombinantly produced orcollected from naturally occurring sources.

[0280] Features of the invention are set forth in the following claims.

We claim:
 1. A collection system comprising a separation chamber thatreceives blood or a suspension containing red blood cells and performs aseparation process including separation of red blood cells from theblood or the suspension, the separation chamber containing, during theseparation process, a red blood cell volume, an outlet line coupled tothe separation chamber to remove red blood cells from the chamberdevice, at least in part, while the separation process occurs, acollection container coupled to the outlet line to receive a volume ofred blood cells removed from the separation chamber, and a controllerincluding a processing function that, during the separation process,includes comparing the volume of red blood cells received by thecollection container to a selected targeted red blood cell collectionvolume to derive a difference, and another processing function thatincludes purging substantially all the red blood cell volume occupyingthe separation chamber into the collection container when the red bloodcell volume occupying the separation chamber approximates thedifference.
 2. A system according to claim 1 wherein the separationchamber performs the separation process by generating a centrifugalseparation field.
 3. A system according to claim 1 wherein theseparation chamber comprises a body preformed to hold a fixed bloodvolume.
 4. A system according to claim 3 wherein the body of theseparation chamber is preformed by molding.
 5. A system according toclaim 1 wherein the other processing function includes conveying avolume of blood into the separation chamber to displace the red bloodcell volume from the separation chamber.
 6. A system according to claim5 wherein the other processing function includes determining, as afunction of blood hematocrit, red blood cell hematocrit, andconfiguration of the separation chamber, the volume of blood that is tobe conveyed into the separation chamber to displace the red blood cellvolume.
 7. A system according to claim 1 wherein the separation processincludes separation of blood into a plasma volume, the red blood cellvolume, and a leukocyte volume, and wherein the other processingfunction includes purging substantially all the plasma volume and theleukocyte volume from the separation chamber prior to purgingsubstantially all the red blood cell volume from the separation chamber.8. A system according to claim 7 wherein the other processing functionincludes preventing substantially all the plasma volume and theleukocyte volume purged from the separation chamber from entering thecollecting container.
 9. A system according to claim 1 wherein the otherprocessing function includes conveying a volume of blood into theseparation chamber and performing the separation process while purgingthe red blood cell volume from the separation chamber.
 10. A systemaccording to claim 9 wherein the other processing function includesdetermining, as a function of blood hematocrit, red blood cellhematocrit, and configuration of the separation chamber, the volume ofblood that is to be conveyed into the separation chamber to displace thered blood cell volume.
 11. A blood separation system comprising aseparation chamber having a fixed volume that, in use, performs aseparation process including separation of blood into a red blood cellvolume, a plasma volume, and a leukocyte volume, a blood inlet linecoupled to the separation device to convey blood into the separationdevice, at least in part, while the separation process occurs, a plasmaoutlet line coupled to the separation device to convey plasma from theseparation device, at least in part, while the separation processoccurs, a red blood cell outlet line coupled to the separation device toremove red blood cells from the separation device, at least in part,while the separation process occurs, a collection container coupled tothe red blood cell outlet line to receive red blood cells removed fromthe separation chamber, and a controller including a processing functionthat, during the separation process, includes comparing a collectedvolume of red blood cells received by the collection container to aselected targeted red blood cell collection volume to derive adifference, and another processing function that includes purgingsubstantially all the red blood cell volume occupying the separationchamber into the collection container when the red blood cell volumeoccupying the separation chamber approximates the difference.
 12. Asystem according to claim 11 wherein the separation chamber performs theseparation process by generating a centrifugal separation field.
 13. Asystem according to claim 11 wherein the separation chamber comprises abody preformed to hold a fixed blood volume.
 14. A system according toclaim 13 wherein the body of the separation chamber is preformed bymolding.
 15. A system according to claim 11 wherein the other processingfunction includes conveying a volume of blood into the separationchamber to displace the red blood cell volume from the separationchamber.
 16. A system according to claim 15 wherein the other processingfunction includes determining, as a function of blood hematocrit, redblood cell hematocrit, and configuration of the separation chamber, thevolume of blood that is to be conveyed into the separation chamber todisplace the red blood cell volume.
 17. A system according to claim 11wherein the other processing function includes purging substantially allthe plasma volume and all the leukocyte volume from the separationchamber prior to purging substantially all the red blood cell volumefrom the separation chamber.
 18. A system according to claim 17 whereinthe other processing function includes preventing substantially all theplasma volume and all the leukocyte volume purged from the separationchamber from entering the collecting container.
 19. A system accordingto claim 11 wherein the other processing function includes conveying avolume of blood into the separation chamber and performing theseparation process while purging the red blood cell volume from theseparation chamber.
 20. A system according to claim 19 wherein the otherprocessing function includes determining, as a function of bloodhematocrit, red blood cell hematocrit, and configuration of theseparation chamber, the volume of blood that is to be conveyed into theseparation chamber to displace the red blood cell volume.
 21. Acollection method comprising the steps of conveying blood or asuspension containing red blood cells into a separation chamber toperform a separation process including separation of red blood cellsfrom the blood or the suspension, the separation chamber containing,during the separation process, a volume of red blood cells, removing redblood cells from the chamber device, at least in part, while theseparation process occurs, collecting in a collection container a volumeof red blood cells removed from the separation chamber, and performing aprocessing function that, during the separation process, includescomparing the volume of red blood cells that are collected to a selectedtargeted red blood cell collection volume to derive a difference, andperforming another processing function that includes purgingsubstantially all red blood cells occupying the separation chamber intothe collection container when the volume of red blood cells occupyingthe separation chamber approximates the difference.
 22. A methodaccording to claim 21 wherein the separation process includes generatinga centrifugal separation field.
 23. A method according to claim 21wherein the other processing function includes to displace the volume ofred blood cells from the separation chamber.
 24. A method according toclaim 23 wherein the other processing function includes determining, asa function of blood hematocrit, red blood cell hematocrit, andconfiguration of the separation chamber, the volume of blood that is tobe conveyed into the separation chamber to displace the volume of redblood cells.
 25. A method according to claim 21 wherein the separationprocess includes separation of blood into a plasma volume, the volume ofred blood cells, and a leukocyte volume, and wherein the otherprocessing function includes purging substantially all the plasma volumeand the leukocyte volume from the separation chamber prior to purgingsubstantially all the red blood cell volume from the separation chamber.26. A method according to claim 25 wherein the other processing functionincludes preventing substantially all the plasma volume and theleukocyte volume purged from the separation chamber from entering thecollecting container.
 27. A method according to claim 21 wherein theother processing function includes conveying a volume of blood into theseparation chamber and performing the separation process while purgingthe volume of red blood cells from the separation chamber.
 28. A methodaccording to claim 27 wherein the other processing function includesdetermining, as a function of blood hematocrit, red blood cellhematocrit, and configuration of the separation chamber, the volume ofblood that is to be conveyed into the separation chamber to displace thevolume of red blood cells.
 29. A blood separation method comprising thesteps of conveying blood into a separation chamber having a fixed volumeto perform a separation process including separation of blood into a redblood cell volume, a plasma volume, and a leukocyte volume, conveyingblood into the separation device, at least in part, while the separationprocess occurs, conveying plasma from the separation device, at least inpart, while the separation process occurs, removing red blood cells fromthe separation device, at least in part, while the separation processoccurs, collecting in a collection container a volume of red blood cellsremoved from the separation chamber, performing a processing functionthat, during the separation process, includes comparing the volume ofred blood cells collected in the collection container to a selectedtargeted red blood cell collection volume to derive a difference, andperforming another processing function that includes purgingsubstantially all the red blood cell volume occupying the separationchamber into the collection container when the red blood cell volumeoccupying the separation chamber approximates the difference.
 30. Amethod according to claim 29 wherein the separation process generates acentrifugal separation field.
 31. A method according to claim 29 whereinthe other processing function includes conveying a volume of blood intothe separation chamber to displace the red blood cell volume from theseparation chamber.
 32. A method according to claim 31 wherein the otherprocessing function includes determining, as a function of bloodhematocrit, red blood cell hematocrit, and configuration of theseparation chamber, the volume of blood that is to be conveyed into theseparation chamber to displace the red blood cell volume.
 33. A methodaccording to claim 29 wherein the other processing function includespurging substantially all the plasma volume and all the leukocyte volumefrom the separation chamber prior to purging substantially all the redblood cell volume from the Separation chamber.
 34. A method according toclaim 33 wherein the other processing function includes preventingsubstantially all the plasma volume and all the leukocyte volume purgedfrom the separation chamber from entering the collecting container. 35.A method according to claim 29 wherein the other processing functionincludes conveying a volume of blood into the separation chamber andperforming the separation process while purging the red blood cellvolume from the separation chamber.
 36. A method according to claim 35wherein the other processing function includes determining, as afunction of blood hematocrit, red blood cell hematocrit, andconfiguration of the separation chamber, the volume of blood that is tobe conveyed into the separation chamber to displace the red blood cellvolume.